DHA Supplementation and Pregnancy Outcome

描述（由申请人提供）：二十二碳六烯酸（DHA）是ω-3脂肪酸家族的一员;它存在于所有细胞膜中，并在视网膜和大脑中积累特别多。在过去的几十年里，越来越多的证据支持这样一种假设，即DHA可能对妊娠健康和结局以及婴儿期感知和认知功能的产后发育起着重要作用。然而，关于这一主题的先前工作集中在产后补充和早产儿风险的改善;这与证据表明DHA在妊娠期间可能通过母亲饮食摄入在胎儿大脑中积累形成对比。因此，目前的建议是基于这样一种可能性，即产前补充可能是一种特别有效的影响积极怀孕和产后结果的手段。我们的研究团队进行的早期临床试验在妊娠的最后三个月提供了相对较低水平的DHA补充剂（约100 mg/天）。这种补充使妊娠期延长了6天。此外，在该人群的一个子集中，分娩时母亲RBC DHA较高与婴儿认知结果相关（18个月内婴儿注意力更成熟，注意力分散程度更低）。在本申请中，我们提出了一项III期临床试验（随机、双盲、安慰剂对照），补充更多的DHA（600 mg/天vs 100 mg/天）和更长的补充持续时间（妊娠2个月vs 1个月）。这种增加的剂量和暴露时间旨在增加先前临床试验中研究的相同人群的妊娠持续时间和宫内生长。最初提交的审查员认为，婴儿随访会增加研究的价值。修订中包括了广泛的产后随访，旨在确定实验性增加母亲DHA摄入量对婴儿和幼儿视觉和认知结果的影响。审查者表示批准增加产后随访，但是，他们提出了几个关于胶囊摄入依从性的新问题，以及研究产后随访部分可能存在的高损耗，并要求对一些指标进行操作定义。这些问题已在本提案的导言和正文中详细讨论。

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.