DHA Supplementation and Pregnancy Outcome

描述(由申请人提供)：二十二碳六烯酸(DHA)是omega-3脂肪酸家族的成员；它存在于所有细胞膜中，并在视网膜和大脑中大量积累。在过去的几十年里，越来越多的证据支持这样的假设，即DHA可能在怀孕健康和结局以及婴儿出生后感知和认知功能的发展中发挥重要作用。然而，以前关于这一主题的工作主要集中在出生后补充和改善早产儿的风险；这与证据表明DHA在怀孕期间在胎儿大脑中积累形成对比，可能是通过母亲的饮食摄入。因此，目前的提议是基于这样一种可能性，即产前补充可能是影响积极妊娠和出生后结局的一种特别有效的手段。我们的研究团队进行的一项早期临床试验在怀孕的最后三个月提供了相对较低的DHA补充量(约100毫克/天)。这种补充剂使妊娠期延长了6天。此外，在这一人群中的一部分，分娩时母亲RBC DHA较高与婴儿认知结果(婴儿注意力更成熟，婴儿在18个月大时注意力分散较低)有关。在目前的应用中，我们建议进行第三阶段临床试验(随机、双盲、安慰剂对照)，补充更多的DHA(每天600毫克比100毫克)和更长的补充时间(怀孕2个月比1个月)。增加剂量和暴露时间的目的是为了在先前的临床试验中研究的同一人群中延长妊娠期和宫内发育。最初提交的报告的审查者认为，这项研究的价值将通过婴儿随访而增加。修订中包括了广泛的出生后跟踪调查，旨在确定实验性增加母亲DHA摄入量对婴儿和儿童早期视觉和认知结果的影响。审查者表示同意增加的产后随访，然而，他们提出了几个新的问题，涉及胶囊摄入的依从性和研究的产后随访部分可能产生的高消耗量，并要求对一些措施进行操作定义。这些问题已在提案的导言和正文中作了详细阐述。

DESCRIPTION (provided by applicant): Docosahexaenoic acid (DHA) is a member of the omega-3 fatty acid family; it is found in all cell membranes, and is accumulated in especially large quantities in the retina and brain. Over the past decades, evidence has accumulated in support of the hypothesis that DHA may have an important role in pregnancy health and outcome, as well as in the postnatal development of perceptual and cognitive function in infancy. However, prior work on this topic has focused on postnatal supplementation and the amelioration of risk in premature infants; this is in contrast to evidence indicating that DHA is accumulated in the fetal brain during gestation, probably through maternal dietary intake. The current proposal is therefore based on the possibility that prenatal supplementation may be an especially efficacious means of affecting positive pregnancy and postnatal outcomes. An earlier clinical trial conducted by our research team provided a relatively low level of DHA supplementation (approximately 100 mg/day) during the last trimester of pregnancy. This supplementation produced an increase of 6 days in the duration of gestation. In addition, higher maternal RBC DHA at delivery in a subset of this population was related to infant cognitive outcomes (more mature infant attention and lower infant distractibility through 18 months of age). In the current application, we propose a Phase III Clinical Trial (randomized, double blind, placebo-controlled) with a larger supplement of DHA (600 mg/day vs 100 mg/day) and longer duration of supplementation (2 vs 1 trimester of pregnancy). This increased dosage and period of exposure is designed to increase gestation duration and intrauterine growth in the same population studied in the previous clinical trial. Reviewers of the initial submission felt the value of the study would be increased by infant followup. An extensive postnatal followup was included in the revision, designed to determine the effect of experimentally increasing maternal DHA intake on visual and cognitive outcomes in infancy and early childhood. Reviewers indicated approval of the added postnatal followup, however, they raised several new questions about compliance with capsule intake and possibly high attrition from the postnatal followup portion of the study and requested operational definitions of some measures. These have been addressed here in detail in the Introduction and body of the proposal.