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（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和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，该计划旨在通过在怀孕期间补充二十二碳六烯酸（DHA）来减少产前压力对婴儿健康和发育的负面影响。DHA是ω-3脂肪酸家族的长链多不饱和脂肪酸成员。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，低水平的膳食DHA摄入量与对压力的次优反应有关，而DHA补充剂可以调节压力反应。目的：这项拟议研究的目的是测试怀孕期间补充DHA是否与1）改善生活在城市贫困中的非洲裔美国妇女怀孕期间的孕产妇健康有关; 2）改善婴儿出生和神经发育结果，以及3）孕期补充DHA与婴儿结局之间的关联是否部分由孕期母体感知压力和压力反应性的降低介导。方法：162名生活在城市贫困中的非洲裔美国孕妇，每周食用少于两份鱼，将被随机分配接受450 mg/天的DHA或安慰剂，从妊娠9-12周开始，直到妊娠结束。将在基线和妊娠24、30和36周时评估感知压力、压力性生活事件、焦虑和抑郁、炎症标志物、DHA水平和对实验室压力源的反应。新生儿结局（例如，胎龄、出生体重、分娩并发症），并在1、4和9个月大时评估婴儿神经发育结果和应激反应。研究者：该应用建立在最近完成的NICHD/NIMH资助的R21（PI：Keenan）的基础上，该研究提供了初步证据，表明怀孕期间补充DHA可以减少生活在低收入城市环境中的怀孕非洲裔美国妇女的感知压力和皮质醇对压力的反应。Keenan和Hipwell博士以及Wroblewksi女士是R21的研究者，并将继续在拟议的研究中合作。Della Torre博士是芝加哥大学的产科助理教授，专门为居住在芝加哥南部的非洲裔美国妇女提供临床服务。创新：这将是第一项大型随机对照研究，研究生活在城市贫困地区的非洲裔美国孕妇补充DHA对母婴健康和压力反应的影响。影响：如果DHA补充剂与感知压力的减少，更调制的母体皮质醇对压力的反应，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，那么可以启动一项关于这些关联演变机制的综合研究计划，并可以实施针对弱势人群中的孕产妇和儿童的基础广泛的预防干预措施，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.