母亲补充胆碱可减轻酒精暴露对新生儿脑容量的影响。
Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes.
机构信息
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Biomedical Engineering Research Centre, Division of Biomedical Engineering, University of Cape Town, Cape Town, South Africa.
出版信息
Alcohol Clin Exp Res. 2021 Sep;45(9):1762-1774. doi: 10.1111/acer.14672. Epub 2021 Aug 18.
BACKGROUND
Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory.
METHODS
Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII.
RESULTS
Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory.
CONCLUSIONS
High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans.
背景
产前酒精暴露（PAE）与较小的区域和全球脑体积有关。在大鼠中，妊娠期胆碱补充可减轻乙醇暴露的发育不良影响。我们最近的一项随机、双盲、安慰剂对照的母体胆碱补充试验表明，在产后 6.5 个月和 12 个月时，婴儿的体部和功能结果得到改善。在这里，我们研究了母体胆碱补充是否能保护新生儿的大脑免受 PAE 相关的体积减少的影响，如果是这样，这些体积变化是否与婴儿识别记忆的改善有关。
方法
52 名出生于重度饮酒妇女的婴儿参加了一项妊娠期间的胆碱补充试验，在 3T 西门子 Allegra MRI 上进行了多回波 FLASH 协议的结构磁共振成像（中位数年龄为产后 2.8 周）。皮质下区域手动分割。在 12 个月时，使用 Fagan 婴儿智力测试（FTII）评估识别记忆。我们检查了胆碱对区域脑体积的影响，胆碱相关的体积增加是否与更高的 FTII 分数有关，以及区域体积增加在多大程度上介导了胆碱对 FTII 的影响。
结果
50 名婴儿（胆碱：n=27；安慰剂：n=23）获得了可使用的 MRI 数据。在胆碱组中，有 12 个区域中的 6 个区域的归一化体积大于安慰剂组（t≥2.05，p≤0.05），并且与母体胆碱依从性的程度相关（β≥0.28，p≤0.04）。右壳核和胼胝体体积较大与 FTII 分数较高相关（r=0.36，p=0.02），并且胆碱对识别记忆的影响存在部分中介作用。
结论
妊娠期间高剂量胆碱补充减轻了 PAE 相关的区域体积减少，较大的体积与 12 个月时的识别记忆改善有关。这些结果首次提供了证据表明，胆碱可能对人类 PAE 相关的脑结构缺陷具有神经保护作用。
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