Feasibility of oral lactoferrin to prevent iron deficiency anemia in obese pregnancy

摘要 母亲缺铁性贫血（IDA）增加不良妊娠结局的风险， 影响新生儿的铁营养，可能对神经发育造成不可逆的有害影响。 为了避免怀孕期间的IDA，女性普遍每天口服含有约27毫克铁的补充剂。 然而，越来越多的人担心这种一刀切的方法对患有糖尿病的妇女的有效性。 全身性炎症，包括肥胖妇女。肥胖女性的铁调素会受到干扰- 膜铁转运蛋白复合物认为铁来自饮食，包括补充铁，并且身体储存较少的生物可利用性。这 表明迫切需要开发和测试新的方法来预防肥胖妇女中的孕产妇IDA。 在这项规划拨款申请中，我们将开发临床和研究基础设施，以测试初步的 口服牛乳铁蛋白（bLf）补充剂预防肥胖妇女母体IDA的有效性。 乳铁蛋白是在哺乳动物的分泌物（包括乳汁）中发现的天然化合物，并且是重要的免疫调节剂。 由于其对炎症和铁调素-膜铁转运蛋白复合物的作用，其是身体铁平衡的调节剂。每日口服 已证明bLf在治疗患有IDA的孕妇中上级口服铁补充剂。 但尚未研究其预防妊娠期IDA的能力。本临床的具体目标 试验计划拨款包括：1）建立临床和研究基础设施，以招募、登记和随机化 有IDA风险的肥胖妇女在怀孕期间接受口服bLf干预。为此，我们将建立、测试、完善和 完成临床和研究基础设施和实施程序，包括提供者转介 系统、实时依从性监测和数据基础设施; 2）随机对照试验的初步测试 在40名孕妇中， 肥胖有患缺铁性贫血的风险。在这一目标中，我们试图了解招聘，坚持和保留率， 干预的可接受性，以确定对母体炎症和母体 以及新生儿铁和血液学相关标志物。这项研究将首次提供必要的数据， 足以告知和开发口服bLf作为安全和可扩展的天然化合物的大规模疗效试验 预防肥胖妇女的缺铁性贫血。最终如果成功，这个项目是重要的第一步 旨在改善占育龄妇女三分之一以上的肥胖妇女的产前护理 在美国

ABSTRACT Maternal iron deficiency anemia (IDA) increases the risk of adverse pregnancy outcomes and can negatively impact the iron endowment of the neonate that may cause irreversible deleterious effects on neurodevelopment. To avert IDA in pregnancy, women are universally prescribed a daily oral supplement containing ~27 mg of iron. However, there is growing concern regarding the efficacy of this one-size-fits-all approach for women with systemic inflammation, including women with obesity. Obese women experience disruption to the hepcidin- ferroportin complex deeming iron from diet, including supplemental iron, and body stores less bioavailable. This indicates an urgent need to develop and test new methods to prevent maternal IDA among women with obesity. In this planning grant application, we will develop the clinical and research infrastructure to test the preliminary efficacy of oral bovine lactoferrin (bLf) supplementation for the prevention of maternal IDA among obese women. Lactoferrin is a natural compound found in secretions from mammals, including milk, and is an important regulator of body iron balance given its effects on inflammation and the hepcidin-ferroportin complex. Daily oral bLf has been shown to be superior to oral iron supplementation for treating IDA in pregnant women with inflammation but has not been studied for its ability to prevent IDA in pregnancy. The specific aims of this clinical trial planning grant include: 1) Establish the clinical and research infrastructure to recruit, enroll, and randomize obese women at risk of IDA to an oral bLf intervention in pregnancy. In this aim we will establish, test, refine and finalize the clinical and research infrastructure and implementation procedures, including a provider referral system, real-time adherence monitoring, and data infrastructure; and 2) Pilot test a randomized controlled trial of oral bLf supplementation from early second trimester up through delivery among 40 pregnant women with obesity at risk of IDA. In this aim we seek to understand recruitment, adherence, and retention rates and intervention acceptability to determine feasibility and preliminary efficacy on maternal inflammation and maternal and neonatal iron and hematological-related markers. This study will provide first of its kind data, necessary and sufficient to inform and develop a large-scale efficacy trial of oral bLf as a safe and scalable natural compound for the prevention of IDA among obese women. Ultimately if successful, this project is an important first step toward improving prenatal care for obese women who represent more than a third of reproductive-age women in the United States.