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

描述(申请人提供)：二十二碳六烯酸(DHA，22：6n-3)是n-3脂肪酸家族中的一种长链多不饱和脂肪酸成员。DHA在早期发育中是重要的，无论是在妊娠的生殖生理方面，还是在出生后的行为和认知功能方面。在成年人中，DHA被证明可以降低甘油三酯，对心血管健康和自主神经控制很重要，可以降低心率(HR)和血压，增加心率变异性(HRV)。然而，人们对n-3脂肪酸如何影响婴儿、儿童或胎儿的心脏自主神经控制知之甚少。在使用非侵入性胎儿生物磁力仪记录和表征胎儿自主神经对心率和变异性的控制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品DHA补充剂的妇女。在这个小样本中，我们发现较低的胎心率和较高的胎心率变异性。这表明孕妇孕期摄入DHA可能对胎儿心脏自主神经控制产生影响，从而导致平均心率降低和心率变异性升高。到目前为止，还没有人调查孕妇在怀孕期间补充DHA对胎儿心率和变异性测量的影响。本项目的具体目的是评估孕妇在怀孕第二和第三个三个月期间补充DHA对孕妇和胎儿心率和变异性的测量以及孕24周和36周胎儿运动的影响。此外，我们计划进行一项出生后评估，以确定补充剂对新生儿神经行为组织、婴儿心率和迷走控制的影响。这项建议旨在验证一种假设，即妊娠最后两个月期间给予母亲DHA(每天600 mg)会增加母亲红细胞磷脂DHA，从而对胎儿心脏自主神经调节产生积极影响，反映在更高的迷走神经控制力(HR降低)和HRV增加。DHA将通过藻油胶囊提供，而安慰剂组将提供含有大豆油和玉米油的胶囊。这项建议的新颖之处在于：1)这是第一次纵向探索确定怀孕期间补充DHA对心脏自主神经系统控制的影响，从胎龄24周到出生后2个月。2)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，非常适合同时测量母婴心磁图(MCG)和胎儿运动与公共卫生的相关性：最佳的胎儿神经发育依赖于完全来自饮食来源的营养，包括二十二碳六烯酸(DHA)。补充DHA对公众健康具有普遍意义，因为对成年人的研究表明，饮食摄入DHA会影响几种心血管疾病风险指标，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的编程、心脏调节和未来的心脏健康具有重要意义。

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.