Improving maternal and child health through prenatal fatty acid supplementation: A randomized controlled study in African American women living in low-income urban environments

 描述(申请人提供)：生活在贫困中的孕妇经常经历长期的压力，因此压力荷尔蒙水平较高。在子宫内暴露于高水平的压力荷尔蒙会对发育中的胎儿以及婴儿的情绪和行为调节能力产生负面影响。在本申请中，我们描述了一项正在开发的研究计划，旨在通过在怀孕期间补充二十二碳六烯酸(DHA)来减少产前应激对婴儿健康和发育的负面影响。DHA是omega-3脂肪酸家族中的一种长链多不饱和脂肪酸。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，饮食中低水平的DHA摄入量与对压力的次优反应有关，补充DHA可以调节压力反应。目的：这项拟议研究的目标是测试怀孕期间补充DHA是否与1)生活在城市贫困中的非裔美国妇女在怀孕期间改善母亲健康有关；2)改善婴儿出生和神经发育结果；3)怀孕期间补充DHA与婴儿结果之间的联系是否部分地通过减少母亲感觉到的压力和怀孕期间的压力反应来调节。方法：162名生活在城市贫困中的非洲裔美国孕妇每周食用不到两份鱼，她们将被随机分配到从怀孕9-12周开始每天服用450毫克的DHA或安慰剂，直到怀孕结束。将在基线、怀孕24周、30周和36周时评估感知的压力、应激性生活事件、焦虑和抑郁、炎症标志物、DHA水平和对实验室应激源的反应。新生儿结局(例如，胎龄、出生体重、分娩并发症)将从医疗记录中收集，婴儿的神经发育结局和应激反应将在1、4和9个月大时进行评估。研究人员：这项应用建立在最近完成的由NICHD/NIMH资助的R21(PI：KENAN)的基础上，该研究产生了初步证据，表明在怀孕期间补充DHA可以减少生活在低收入城市环境中的怀孕的非裔美国妇女感受到的压力和皮质醇对压力的反应。基南博士、希普韦尔博士和沃布洛夫斯基女士是R21的研究人员，他们将继续合作开展拟议中的研究。Della Torre博士是芝加哥大学产科助理教授，专门为居住在芝加哥南部的非洲裔美国女性提供临床服务。创新：这将是首次对生活在城市贫困中的怀孕的非洲裔美国妇女补充DHA对母婴健康和压力反应的影响的大型随机对照研究。影响：如果补充DHA与感知压力的减少、母亲对压力的更有调节的皮质醇反应以及婴儿更优化的情绪和行为调节有关，即使在城市贫困的背景下，也可以启动关于这些关联演变机制的全面研究计划，并可以实施针对脆弱人群中的母婴的广泛预防干预措施，这可能会减少美国的健康差距。

 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 the infant's capacity for emotion and behavioral regulation. In this application 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 test whether DHA supplementation during pregnancy is associated with 1) improved maternal health during pregnancy among African American women living in urban poverty; 2) improved infant birth and neurodevelopmental outcomes, and 3) whether the association between DHA supplementation during pregnancy and infant outcomes is partially mediated by reductions in maternal perceived stress and stress reactivity during pregnancy. Approach: One hundred sixty-two pregnant African American women living in urban 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 9-12 weeks of gestation through the end of pregnancy. Perceived stress, stressful life events, anxiety, and depression, inflammatory markers, DHA levels and response to a laboratory stressor will be assessed at baseline and at 24, 30, and 36 weeks of pregnancy. Neonatal outcomes (e.g., gestational age, birth weight, delivery complications) will be collected from medical records, and infant neurodevelopmental outcomes and stress reactivity will be assessed at 1, 4 and 9 months of age. Investigators: This application builds on a recently completed NICHD/NIMH funded R21 (PI: Keenan), which yielded preliminary evidence that DHA supplementation during pregnancy reduces perceived stress and cortisol response to stress in pregnant African American women living in low-income, urban environments. Drs. Keenan and Hipwell and Ms. Wroblewksi were investigators on the R21 and will continue to work together on the proposed study. Dr. Della Torre is an Assistant Professor of Obstetrics at the University of Chicago, who specializes in providing clinical services to African American women living in the south side of Chicago. Innovation: This will be the first large randomized controlled study of the effect of DHA supplementation in pregnant African American women living in urban poverty on maternal and infant health and stress response. Impact: 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 urban poverty, then a comprehensive program of research on the mechanisms by which these associations evolve can be launched and broad-based prevention interventions that target maternal and child in vulnerable populations can be implemented, potentially leading to reductions health disparities in the U.S.