The Effects of Docosahexaenoic acid (DHA) on fetal cardiac outcomes

描述（由申请人提供）：二十二碳六烯酸（DHA，22：6n-3）是n-3脂肪酸家族的长链多不饱和脂肪酸成员。DHA在早期发育中很重要，无论是在妊娠期的生殖生理学方面，还是在出生后的行为和认知功能方面。在成人中，DHA已被证明可以降低甘油三酯，对心血管健康和自主控制，降低心率（HR）和血压以及增加心率变异性（HRV）非常重要。然而，关于n-3脂肪酸如何影响婴儿、儿童或胎儿的心脏自主控制知之甚少。在使用非侵入性胎儿生物磁力计记录和表征胎儿自主控制心率和变异性以及其他神经行为的过程中，我们确定了一组在怀孕期间服用商业DHA补充剂的妇女。在这个小样本中，我们发现胎儿心率较低，胎儿心率变异性较高。这表明母亲在怀孕期间摄入DHA可能对胎儿心脏自主控制产生影响，导致平均心率降低和心率变异性升高。到目前为止，还没有人研究过母亲在怀孕期间补充DHA对胎儿心率和变异性的影响。该项目的具体目的是评估在妊娠第2和第3个三个月期间母亲补充DHA对母亲和胎儿心率和变异性以及胎龄24和36周时胎动的影响。此外，我们计划进行产后评估，以确定补充对新生儿神经行为组织和婴儿心率和迷走神经控制的影响。该建议旨在检验以下假设：在妊娠的最后两个三个月期间给予母体DHA摄入量（每天600 mg）将增加母体红细胞磷脂DHA，从而对胎儿心脏自主神经系统调节产生积极影响，反映在更高的迷走神经控制（降低HR）和增加HRV。DHA将通过藻油胶囊提供，而安慰剂组将提供含有大豆和玉米油组合的胶囊。这一提议的新颖之处在于：1）这是首次纵向探索，以确定母亲在怀孕期间补充DHA对心脏自主神经系统控制率和变异性的影响，从孕龄24周至产后2个月; 2）这是首次探索怀孕期间补充DHA对新生儿神经行为组织的影响; 3）它使用了一种新的技术，该技术非常适合于同时测量母亲和胎儿的心磁图（MCG）和胎动。公共卫生相关性：最佳的胎儿神经发育依赖于完全来自饮食来源的营养素，包括二十二碳六烯酸（DHA）。DHA补充剂具有普遍的公共健康利益，因为成年人的研究表明，DHA的饮食摄入会影响几种心血管疾病风险标志物，包括血压和心率。这项研究的结果可能对母婴营养、胎儿自主神经系统控制程序、心脏调节和未来心脏健康有重要意义。

DESCRIPTION (provided by applicant): Docosahexaenoic acid (DHA, 22:6n-3) is a long-chain polyunsaturated fatty acid member of the n-3 fatty acid family. DHA is important in early development, both in terms of the reproductive physiology of gestation and in postnatal behavioral and cognitive function. In adults, DHA has been shown to lower triglycerides and is important to cardiovascular health and autonomic control, lowering heart rate (HR) and blood pressure and increasing heart rate variability (HRV). However, very little is known about how n-3 fatty acids impact cardiac autonomic control in infants, children or the fetus. In the course of using a non-invasive fetal biomagnetometer to record and characterize aspects of fetal autonomic control of heart rate and variability and other neurobehaviors, we identified a group of women who were taking commercial DHA supplements during their pregnancy. In this small sample, we found lower fetal heart rate and higher fetal heart rate variability. This suggests that maternal DHA intake during pregnancy may have an effect on fetal cardiac autonomic control that results in lower mean heart rate and higher heart rate variability. To date, no one has investigated the effects of maternal DHA supplementation during pregnancy on fetal cardiac measures of rate and variability. The specific aims of this project are to evaluate the effect of maternal DHA supplementation during the 2nd and 3rd trimesters of pregnancy on maternal and fetal cardiac measures of rate and variability and fetal movements at 24 and 36 weeks gestational age. Additionally, we plan a postnatal assessment to determine the effect of supplementation on newborn neurobehavioral organization and infant heart rate and vagal control. This proposal is designed to test the hypothesis that maternal DHA intake (600 mg per day) given during the last two trimesters of pregnancy will increase maternal red blood cell phospholipid DHA and thus will have a positive influence on fetal cardiac autonomic nervous system regulation reflected in higher vagal control (reduced HR) and increased HRV. DHA will be provided via algal oil capsules while the placebo group will be provided capsules containing a combination of soybean and corn oils. This proposal is novel in that: 1) it is the first longitudinal exploration to determine the effects of maternal DHA supplementation during pregnancy on cardiac autonomic nervous system control of rate and variability from the 24 weeks gestational age to 2 months postnatal age 2) it is the first to explore the effects of supplementation during pregnancy on newborn neurobehavioral organization and 3) it uses a novel technology that is well suited to simultaneously measure the maternal and fetal magnetocardiogram (MCG) and fetal movements PUBLIC HEALTH RELEVANCE: Optimal fetal neurodevelopment is dependent on nutrients exclusively derived from dietary sources, including docosahexaenoic acid (DHA). DHA supplementation is of general public health interest because studies in adults have shown that dietary intake of DHA affects several cardiovascular disease risk markers including blood pressure and heart rate. The results of this study may have significant implications in regard to maternal- fetal nutrition, fetal programming of autonomic nervous system control, cardiac regulation and future cardiac health.