Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in quail embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 weeks of human gestation) regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared to controls, while embryos given FA with ethanol had significantly reduced regurgitant blood flow but did not return to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects is warranted.

中文翻译：

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叶酸可预防因产前乙醇暴露引起的功能性和结构性心脏缺陷


回流血流量增加与心内膜垫缺陷和由此产生的先天性心脏病（CHD）有关。产前酒精暴露 (PAE) 已被证明会改变早期血流，导致心内膜垫异常和先心病 (CHD)。包括叶酸 (FA) 在内的化合物可以减轻 PAE 的影响并预防冠心病，但很少有研究评估它们对血流的影响。我们模拟了鹌鹑胚胎在原肠胚形成时的暴饮暴食。胚胎单独暴露于乙醇，单独暴露于FA（3.2微克/卵），并且两者同时暴露。我们通过多普勒光学相干断层扫描 (OCT) 量化了心脏循环阶段（相当于人类妊娠 4 周）的回流血流量，并使用 OCT 成像量化了心内膜垫体积。还测量了异常身体曲率和心率的发生率。与对照组相比，暴露于乙醇的胚胎显示反流血流量显着增加，而给予乙醇 FA 的胚胎显着减少反流血流量，但没有恢复到对照水平。乙醇暴露导致心内膜垫明显变小、异常，添加 FA 改善了它们的尺寸，但它们仍然小于对照组。 PAE 后身体弯曲异常的发生率有所降低，但 FA 并不能完全预防。补充FA可部分缓解PAE引起的心血管功能和形态异常。正常的血流和心内膜垫都是产生健康的四腔心脏所必需的。这些发现表明，FA 补充剂应在怀孕早期开始，以预防心脏和神经管缺陷。有必要研究化合物组合预防 PAE 引起的缺陷的功效。