Prevention of Developmental Delay and Xylitol (PDDaX) Study

全球每年发生1500万早产，其中大多数出生在低收入和中等收入国家。 早产是5岁以下儿童死亡和未来神经发育迟缓的主要原因。一个很长的- 牙周病和早产之间存在既定的联系，但常见的牙科干预措施，如 调整和规划并不能防止早产。木糖醇，一种常见于口香糖产品中的糖替代品， 通过假定抑制局部和全身炎症来预防龋齿和牙周炎，这是 子代神经发育迟缓。我们最近在马拉维完成了一项整群随机试验，旨在 测试木糖醇口香糖预防早产和新生儿结局的效果。这项后续研究 一项提案旨在通过评估是否接触木糖醇胶来有意义地推进我们的发现 先入为主或在怀孕早期改善后代的神经发育结果(长达6岁 年龄)。具体地说，我们将通过正式评估咀嚼木糖醇口香糖是否可以防止 利用预防早产儿和木糖醇的受试者的不良神经发育结局 (PPaX)试验，2015-2019年在马拉维招募了10,404名孕妇。 研究的具体目的是：1)通过比较评价MDAT的敏感性和特异性 应用KABC-II神经发育诊断工具评估早产儿神经发育迟缓 4-6岁儿童；2)评估MDAT的敏感性和特异性，并与KABC- 2)评估4-6岁早产儿神经发育迟缓；3)确定 孕期接触木糖醇口香糖对200例性别匹配足月孕妇神经发育结局的影响 出生儿童(100名对照组，100名木糖醇)和200名早产儿(100名对照组，100名木糖醇)。正在验证 早产儿和足月儿MDAT与KABC-II神经发育评估的比较 马拉维将在未来开展更有效率、更具成本效益的研究，并在资源匮乏的情况下建设能力。 以便更容易地识别神经发育迟缓儿童，并提供更及时的干预。如果使用木糖醇 在怀孕期间被发现可以防止后代的神经发育延迟，这一低成本的解决方案将被证明 在全球范围内预防神经发育延迟方面成为游戏规则的改变者。 建议的职业和学习目标是：1)掌握流行病学、研究设计、数据方面的高级技能 管理和分析方法，以正确实施以评估新生儿结局为重点的研究 2)提高数据库开发、科学写作、演示文稿、 和助学金准备，以及3)获得高级技能，包括神经发育测试选择、考官 进行严格的神经发育所需的培训和监督、测试解释和知识 结果研究。这些技能将促进申请人在围产期干预方面的尖端研究 改善最脆弱人群的新生儿健康和未来的神经发育结果。

Globally, 15 million preterm births occur annually, with the majority born in low- and middle-income countries. Prematurity is a leading cause of both under-5 mortality and future neurodevelopmental delay. A long- established link between periodontal disease and preterm birth exists, yet common dental interventions such as scaling and planing fail to prevent preterm birth. Xylitol, a sugar substitute commonly found in gum products, prevents caries and periodontitis with presumed dampening of local and systemic inflammation, a risk factor for neurodevelopmental delay in offspring. We recently completed a cluster-randomized trial in Malawi designed to test the efficacy of xylitol gums to prevent preterm birth and immediate neonatal outcomes. This follow-up study proposal seeks to meaningfully advance our findings by evaluating if exposure to xylitol gum administered preconception or during early pregnancy improves neurodevelopmental outcomes in offspring (up to 6 years of age). Specifically, we will test the hypothesis by formally evaluating whether chewing xylitol gum prevents adverse neurodevelopmental outcomes by leveraging subjects from the Prevention of Prematurity and Xylitol (PPaX) Trial that enrolled 10,404 pregnant women in Malawi from 2015-2019. The Specific Aims of the research are to: 1) Evaluate the sensitivity and specificity of the MDAT as compared to the KABC-II neurodevelopment diagnostic tool in assessing neurodevelopmental delay of formerly term children aged 4-6 years of age; 2) Evaluate the sensitivity and specificity of the MDAT as compared to the KABC- II in assessing neurodevelopmental delay of formerly preterm children aged 4-6 years of age; 3) Determine the impact of xylitol gum exposure during pregnancy on the neurodevelopmental outcomes of 200 sex-matched term born children (100 controls, 100 xylitol) and 200 preterm born children (100 controls, 100 xylitol). Validating the MDAT by comparing it to the KABC-II neurodevelopmental assessment in former preterm and term neonates in Malawi will allow for more efficient, cost-effective studies in the future and build capacity in low-resourced settings to identify children with neurodevelopmental delay more easily and provide more timely intervention. If xylitol use during pregnancy is found to prevent neurodevelopmental delay in offspring, this low-cost solution will prove to be a game-changer in preventing neurodevelopmental delay worldwide. Proposed Career and Learning Objectives are to: 1) Attain advanced skills in epidemiology, study design, data management, and analytic methods to correctly implement research focusing on evaluating neonatal outcomes in settings of health disparities, and 2) Enhance skills in database development, scientific writing, presentations, and grant preparation, and 3) Attain advanced skills, including neurodevelopmental test selection, examiner training and oversight, test interpretation and knowledge needed to conduct rigorous neurodevelopmental outcomes research. These skills will facilitate the applicant’s cutting-edge research on perinatal interventions to improve neonatal health and future neurodevelopmental outcomes in the most vulnerable populations.