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

 描述（由申请方提供）：美国成年人的DHA摄入量较低，α-亚麻酸（18：3 n-3）转化为DHA（22：6 n-3）的转化率也较低。因此，美国女性怀孕时的DHA水平低于发达国家的其他国家，这表明可能缺乏一种重要的营养素，这种营养素已被证明可以减少炎症。这项III期临床试验（随机、双盲和安慰剂对照）的目标是检验以下主要假设：在妊娠的一半期间，向美国妇女补充1000 mg二十二碳六烯酸（DHA），比目前许多产前营养补充剂（约200 mg）的量高800 mg，可以减少早期早产（ePTB）（<34周）。妊娠）。这是一项在当前提案所依据的一个拟定研究中心进行的美国试验（RO 1 HD 047315，ClinicalTrials.gov ID：NCT 00266825）的有利次要结局。次要结局包括出生体重<1500 g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%的功效来检测估计938名受试者的假设结果，如果在研究计划结束前观察到强结果（概率>0.995），则允许研究提前停止，并将60%的参与者置于更好的DHA剂量。传统的90%功效的平等随机化需要1200名受试者，时间更长，并且仅将50%的参与者置于更好的DHA剂量。这项拟议的研究有可能确定在怀孕期间补充DHA是否可以降低ePTB的发病率，这是一个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发现。

 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.