Docosahexaenoic Acid (DHA) Supplementation in Pregnancy to Reduce Early Preterm Birth

 描述(申请人提供)：美国成年人的二羟甲酸摄入量很低，α-亚麻酸(18：3n-3)转化为dHA(22：6n-3)的转化率也很低。其结果是，与发达国家相比，美国妇女怀孕时DHA水平较低，这表明一种已被证明可减少炎症的重要营养物质潜在缺乏。这项第三阶段临床试验(随机、双盲和安慰剂对照)的目标是检验一个基本假设，即在怀孕一半期间补充美国妇女1000毫克的二十二碳六烯酸(DHA)，比目前许多产前营养补充剂的量(~200毫克)高800毫克，可以减少早产(EPTB)(34周)。怀孕)。这是美国试验(RO1 HD047315，临床试验ID：NCT00266825)的一个有利的次要结果，该试验在一个建议的研究地点进行，目前的提议是以此为基础进行的。次要结局包括出生体重及体重1500克和妊娠结局(先兆子痫、妊娠期糖尿病、剖腹产)。我们提出了一种贝叶斯自适应设计，具有90%的能力来检测假设的结果，估计938名受试者，允许研究提前停止，如果在研究预定结束之前观察到较强的结果(概率&>0.995)，并将60%的参与者置于较好的DHA剂量。传统的90%功率的等量随机试验需要1200名受试者，时间更长，只有50%的参与者服用更好的DHA剂量。这项拟议的研究有可能确定怀孕期间补充DHA是否可以降低EPTB的发病率，EPTB是一种严重的公共卫生问题，具有巨大的社会和家庭成本。随机化设计有可能显著加快研究社区和临床实践的研究结果。

 DESCRIPTION (provided by applicant): DHA intake of US adults is low and conversion of α-linolenic acid (18:3n-3) to DHA (22:6n-3) is also low. As a result US women enter pregnancy with lower DHA status than other countries in the developed world suggesting a potential deficiency of an important nutrient that has been shown to reduce inflammation. The goal of this Phase III Clinical Trial (randomized, double-blind, and placebo-controlled) is to test the primary hypothesis that supplementing US women with 1000 mg of docosahexaenoic acid (DHA), 800 mg above the amount currently in many prenatal nutritional supplements (~200 mg) during the half of pregnancy can reduce early preterm birth (ePTB) (<34 wk. gestation). This was a favorable secondary outcomes of a US trial (RO1 HD047315, Clinical Trials.gov ID: NCT00266825) conducted at one of the proposed study sites on which the current proposal is modeled. Secondary outcomes include birth weight <1500g and pregnancy outcomes (preeclampsia, gestational diabetes, C-section delivery). We propose a Bayesian Adaptive Design with 90% power to detect the hypothesized outcomes with an estimated 938 subjects that allows the study to stop early if strong results (probability >0.995) are observed before the study is scheduled to end and places 60% of the participants on the better DHA dose. Conventional equal randomization with 90% power would require 1200 subjects, be longer, and place only 50% of the participants on the better DHA dose. The proposed study has the potential to determine if nutritional supplementation with DHA during pregnancy can reduce the incidence of ePTB, a serious public health problem with large societal and family costs. The randomization design has the potential to significantly expedite findings to the research community and clinical practice.