Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants

早产儿唾液基因表达和口服喂养的体感调节

• 批准号: 9007202
• 负责人: STEVEN M BARLOW
• 金额: $ 60.41万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9007202
• 关键词: Achievement; Address; Age; Assessment tool; Bayesian Modeling; Biological Markers; Boston; Bronchopulmonary Dysplasia; Caregivers; Charge; Childhood; Clinical; Clinical Trials; Computer Analysis; Cutaneous; Data; Development; Devices; Enrollment; FDA approved; Feeding behaviors; Feeds; Frequencies; Gene Expression; Gene Expression Profile; Genes; Gestational Age; Goals; Growth; Health; Home environment; Impairment; Infant; Intervention; Knowledge; Laboratories; Learning; Long-Term Effects; Medical; Medical center; Molecular; Molecular Profiling; Monitor; Morbidity - disease rate; Multicenter Trials; National Institute of Child Health and Human Development; Neonatal; Neonatal Intensive Care Units; Oral; Oral cavity; Outcome; Pacifiers; Polymerase Chain Reaction; Population; Populations at Risk; Predisposition; Pregnancy; Premature Infant; Process; Questionnaires; Randomized; Readiness; Research Proposals; Reverse Transcription; Risk; Saliva; Salivary; Sampling; Staging; Technology; Testing; Time; WNT3 gene; aged; base; blind; critical developmental period; feeding; improved; innovation; innovative technologies; insight; medical complication; neonate; neurodevelopment; non-nutritive sucking; novel; nutrition; personalized approach; personalized care; predictive modeling; preterm newborn; public health relevance; responders and non-responders; response; salivary gene; sex; skills; somatosensory; success; treatment group; treatment response; treatment strategy

 DESCRIPTION (provided by applicant): Extremely preterm infants (EPIs) (< 28 weeks' gestation) have increased susceptibility for multiple significant short- and long-term medical complications that significantly delay the development of essential milestones, such as oral feeding, required for discharge. Further, infants who develop bronchopulmonary dysplasia (BPD) are at even greater risk for oral feeding difficulties compared to gestationally aged matched controls. Despite the frequency of oral feeding difficulties in this at-risk population, there currently exists no objective assessment tool to predict when an infant may safely feed by mouth and only limited intervention strategies to improve feeding behavior. The overall goal of this research proposal is to pair the expertise of Co-PIs Drs. Steven Barlow and Jill Maron to develop an innovative, novel, personalized and integrative approach that directly addresses the important need for oral feeding treatment strategies for the EPI population. In this multicenter trial, 180 EPIs will be enrolled from three neonatal intensive care units (CHI Health St. Elizabeth, Lincoln, NE; Tufts Medical Center, Boston, MA; and Santa Clara Valley Medical Center, Santa Jose, CA). Infants will be randomized to receive either PULSED orocutaneous somatosensory stimulation (PULSED NTrainer(r)) previously developed in the Barlow Laboratory, or SHAM (blind pacifier) starting at 30 weeks' post- conceptional age (PCA) up to the achievement of full oral feeds or discharge home. Serial salivary samples (n=2/week) will be obtained concomitantly to examine the gene expression profiles of six biomarkers (AMPK, NPY2R, NPHP4, WNT3, PLXNA1, PLXNA3) previously shown by the Maron Laboratory to be associated with oral feeding success in the premature newborn. In Aim #1, we will test the hypothesis that infants who received PULSED NTrainer(r) intervention will have a shortened duration of time to achieve full oral feeds and that their salivary gene expression profiles will correlate with feeding success. Infants will be stratified based upon their gestational age, sex, and BPD status. In Aim #2, computational analyses of both clinical and gene expression data from Aim #1 will be performed to identify responders and non-responders to the PULSED NTrainer(r) intervention and to identify critical times in neurodevelopment when infants may most benefit from the intervention. Finally in Aim #3, infants will undergo Bayley III Developmental Screen at 18-24 months' PCA to assess both the long-term effect of the PULSED NTrainer(r) on feeding behavior and neurodevelopment and the accuracy of neonatal salivary gene expression profiles to predict impairments later in childhood. Infants will also be assessed with the NICHD NRN 18-month Feeding-Growth-Nutrition Questionnaire to further our understanding of the PULSED NTrainer(r) on long-term growth and feeding behavior.

 描述（由申请人提供）：极早产儿 (EPI)（妊娠 < 28 周）对多种重大短期和长期医疗并发症的易感性增加，这些并发症显着延迟了出院所需的重要里程碑的发展，例如口服喂养。此外，与孕龄匹配的对照相比，患有支气管肺发育不良（BPD）的婴儿面临经口喂养困难的风险更大。尽管这一高危人群经常出现经口喂养困难的情况，但目前还没有客观的评估工具来预测婴儿何时可以安全地经口喂养，并且改善喂养行为的干预策略也很有限。该研究计划的总体目标是将 Co-PI 博士的专业知识结合起来。 Steven Barlow 和 Jill Maron 开发了一种创新、新颖、个性化和综合的方法，直接满足 EPI 人群对口服喂养治疗策略的重要需求。在这项多中心试验中，将从三个新生儿重症监护病房（内布拉斯加州林肯的 CHI Health 圣伊丽莎白；马萨诸塞州波士顿塔夫茨医疗中心；以及加利福尼亚州圣何塞圣克拉拉谷医疗中心）招募 180 名 EPI。从受孕后 (PCA) 30 周开始，婴儿将被随机接受巴洛实验室先前开发的 PULSED 口腔皮肤体感刺激 (PULSED NTrainer(r)) 或 SHAM（盲奶嘴），直至实现完全经口喂养或出院回家。同时将获得系列唾液样本（n=2/周），以检查六种生物标志物（AMPK、NPY2R、NPHP4、WNT3、PLXNA1、PLXNA3）的基因表达谱，Maron 实验室此前已证明这些生物标志物与早产儿经口喂养成功相关。在目标 1 中，我们将检验以下假设：接受 PULSED NTrainer(r) 干预的婴儿实现完全经口喂养的时间会缩短，并且他们的唾液基因表达谱将与喂养成功相关。将根据婴儿的胎龄、性别和 BPD 状况对婴儿进行分层。在目标 #2 中，将对目标 #1 的临床和基因表达数据进行计算分析，以确定对 PULSED NTrainer(r) 干预有反应的人和无反应的人，并确定婴儿可能从干预中获益最多的神经发育关键时刻。最后，在目标 3 中，婴儿将在 18-24 个月的 PCA 时接受 Bayley III 发育筛查，以评估 PULSED NTtrainer(r) 对喂养行为和神经发育的长期影响，以及新生儿唾液基因表达谱的准确性，以预测儿童后期的损伤。还将使用 NICHD NRN 18 个月喂养生长营养问卷对婴儿进行评估，以进一步了解 PULSED NTtrainer(r) 对长期生长和喂养行为的了解。