Impact of Omega-3 Intake During Pregnancy on Maternal Stress and Infant Outcome

描述（由申请人提供）：生活在贫困中的孕妇经常经历慢性压力，因此压力激素水平较高。在子宫内暴露于高水平的应激激素会对发育中的胎儿产生负面影响，后来还会影响婴儿的情绪和行为调节能力。在本提案中，我们描述了一个发展中的研究项目，旨在通过在怀孕期间补充二十二碳六烯酸（DHA）来减少产前压力对婴儿健康和发育的负面影响。DHA是一种长链多不饱和脂肪酸，属于omega-3脂肪酸家族。DHA在神经细胞膜中的浓度最高，影响受体功能、神经递质摄取和信号传递。越来越多的证据表明，低水平的DHA摄入与对压力的次优反应有关，DHA补充可以调节压力反应。目的：拟议研究的目的是探讨孕期补充DHA是否与以下因素有关：1)减少孕期产妇的感知压力；2)在怀孕期间，母亲对压力刺激的皮质醇反应更受调节，3)婴儿对情绪和行为的调节更优。方法：65名生活在市中心贫困地区、每周食用少于两份鱼的孕妇将被随机分配，从妊娠16-20周开始直至妊娠结束，每天服用450毫克DHA或安慰剂。感知压力、妊娠相关压力、生活压力事件、焦虑和抑郁将在基线、妊娠24周、30周和36周以及产后4个月进行评估。将在基线和怀孕36周时评估DHA水平。将在基线、24周和30周测量特里尔社会压力测试的皮质醇反应。产后4个月时，将在实验室评估婴儿气质、认知发展和应激反应。研究者：这一建议来自于关于产前压力和后代心理健康结果的NIMH R21转化科学网络。该网络的三名成员，dr。Keenan， Carter和Glover都是产前压力和儿童心理健康领域的研究人员，这是一个探索性研究的优先领域，可以直接影响临床护理。他们正在合作开发目前的应用程序。创新：这将是第一个关于DHA补充对生活在城市贫困地区的孕妇压力反应影响的随机对照研究，也是第一个关于母亲补充DHA对婴儿情绪和压力调节的研究。相关性：如果DHA补充与感知压力的减少，更有调节的母亲皮质醇对压力的反应，以及婴儿更理想的情绪和行为调节有关，即使在城市贫困的背景下，那么就可以启动一个全面的研究项目，研究这些关联演变的机制，并潜在地广泛预防贫困妇女所生儿童的不良发育结果。公共卫生相关性：这将是首次对生活在市中心贫困地区的孕妇补充必需脂肪酸对怀孕期间应激反应系统的影响进行研究。如果补充必需脂肪酸与减少压力体验、调节激素对压力的反应以及对婴儿情绪和注意力的更优调节有关，即使在城市贫困的背景下也是如此，那么就可以启动一个关于营养对怀孕期间压力作用的综合研究项目。这项研究可能是广泛预防贫困妇女所生儿童发育不良的第一步。

DESCRIPTION (provided by applicant): Pregnant women living in poverty often experience chronic stress, and consequently higher levels of stress hormones. In utero exposure to high levels of stress hormones can negatively affect the developing fetus and later, the infant's capacity for emotion and behavioral regulation. In this proposal we describe a developing program of research designed to reduce the negative impact of prenatal stress on infant health and development via nutritional supplementation of docosahexaenoic acid (DHA) during pregnancy. DHA is a long-chain polyunsaturated fatty acid member of the omega-3 fatty acid family. DHA is found in its highest concentrations in neural cell membranes, affecting receptor function, neurotransmitter uptake, and signal transmission. There is growing evidence that low levels of dietary DHA intake are associated with suboptimal response to stress and that DHA supplementation can modulate stress response. Aims: The goals of the proposed study are to explore whether DHA supplementation during pregnancy is associated with 1) a reduction in maternal perceived stress during pregnancy; 2) a more modulated maternal cortisol response to a stress stimulus during pregnancy, and 3) more optimal regulation of emotion and behavior in the infant. Approach: Sixty-five pregnant women living in inner-city poverty, who consume less than two servings of fish per week, will be randomly assigned to receive 450 mg/daily of DHA or placebo beginning at 16-20 weeks gestation through the end of pregnancy. Perceived stress, pregnancy related stress, stressful life events, anxiety, and depression will be assessed at baseline and at 24, 30, and 36 weeks of pregnancy and at 4 months post-partum. DHA levels will be assessed at baseline and at 36 weeks of pregnancy. Cortisol response to the Trier Social Stress Test will be measured at baseline, 24, and 30 weeks. At 4 months post-partum infant temperament, cognitive development and stress reactivity will be assessed in the laboratory. Investigators: This proposal stems from an NIMH R21 Translational Science Network on prenatal stress and mental health outcomes in the offspring. Three members of that network, Drs. Keenan, Carter, and Glover, are all funded investigators in the area of prenatal stress and child mental health, which is a prioritized area of exploratory research that could directly impact clinical care. They are collaborating on the present application. Innovation: This will be the first randomized controlled study of the effect of DHA supplementation on stress response in pregnant women living in inner-city poverty, and the first study of maternal DHA supplementation on emotion and stress regulation in their infants. Relevance: If DHA supplementation is associated with reductions in perceived stress, more modulated maternal cortisol response to stress, and more optimal emotional and behavioral regulation in the infant, even within the context inner-city poverty, then a comprehensive program of research on the mechanisms by which these associations evolve and the potential for broad-based prevention of poor developmental outcomes among children born to women living in poverty can be launched. PUBLIC HEALTH RELEVANCE: This will be the first study of the effect of essential fatty acid supplementation in pregnant women living in inner-city poverty on the stress response system during pregnancy. If essential fatty acid supplementation is associated with reductions in the experience of stress, more modulated hormonal response to stress, and more optimal regulation of emotion and attention in the infant, even within the context inner-city poverty, then a comprehensive program of research on the role of nutrition on stress during pregnancy can be launched. This study may be the first step toward broad-based prevention of poor developmental outcomes among children born to women living in poverty.