Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants: Randomized Controlled Trial.
Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants: Randomized Controlled Trial.
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DOI：
10.2196/resprot.7712
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发表时间：
2017-06-14
影响因子：
1.7
通讯作者：
Rosner, Austin Oder
中科院分区：
文献类型：
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作者：
Barlow, Steven Michael;Maron, Jill Lamanna;Rosner, Austin Oder
背景技术背景：尽管在高危早产儿的护理方面取得了许多医学进展，但经口喂养仍然是这一脆弱人群面临的第一个也是最先进的神经学挑战之一。客观的，定量的，非侵入性的评估工具，以及神经治疗策略，是非常需要的，以改善喂养和发育的结果。脉冲气动口皮刺激已被证明可以改善表现出延迟或紊乱乳头喂养行为的早产儿的非营养性吸吮（NNS）技能。另外，对新生儿唾液转录组的研究有助于确定与成功的新生儿口服喂养行为直接相关的生物标志物。无创治疗策略和转录组学分析的结合代表了一种经口喂养的综合方法，其中快速的技术进步和个性化的转录组学可以安全地、无创地带到床边，为医疗护理决策提供信息，并改善护理和结果。目的：本研究旨在进行多中心随机对照试验（RCT）在实验概念化方法中结合联合收割机分子和行为方法，以绘制在高危人类新生儿获得经口进食习惯的背景下脉冲体感刺激对唾液基因表达的影响。这项研究的目的是首次尝试将联合收割机无创治疗策略和高危极早产儿（EPI）的转录组学评估结合起来，以（1）改善经口喂养行为和技能，（2）进一步了解与经口喂养相关的生物多样性途径的基因本体，（3）使用基因表达数据来个性化新生儿护理和个性化治疗策略和时机干预，（4）改善长期发育结果。来自三个新生儿重症监护室（NICU）的共180例极早产儿将随机接受PULSED或SHAM（非脉冲）经口皮肤干预，同时每天3次管饲，持续4周，从孕后30周开始。还将每周3次评估婴儿的NNS表现，每周采集多份唾液样本进行转录组学分析，直至婴儿达到完全经口喂养状态。在18个月的校正年龄（CA），婴儿将接受神经发育的后续测试，其结果将与喂养的结果在新生儿和出生后的时期和基因表达数据和干预status.RESULTS：正在进行的美国国立卫生研究院资助的随机对照试验R 01 HD 086088正在积极招募参与者。该研究的预期完成日期为2021年。结论：口腔感觉牵拉干预引起的唾液基因表达差异有望导致早产儿口服喂养诊断和管理的个体化干预措施的发展。试验注册：ClinicalTrials.gov NCT 02696343; https://clinicaltrials.gov/ct2/show/NCT02696343（由WebCite athtp存档：//www.webcitation.org/6r5NbJ9Ym）。
BACKGROUND: Despite numerous medical advances in the care of at-risk preterm neonates, oral feeding still represents one of the first and most advanced neurological challenges facing this delicate population. Objective, quantitative, and noninvasive assessment tools, as well as neurotherapeutic strategies, are greatly needed in order to improve feeding and developmental outcomes. Pulsed pneumatic orocutaneous stimulation has been shown to improve nonnutritive sucking (NNS) skills in preterm infants who exhibit delayed or disordered nipple feeding behaviors. Separately, the study of the salivary transcriptome in neonates has helped identify biomarkers directly linked to successful neonatal oral feeding behavior. The combination of noninvasive treatment strategies and transcriptomic analysis represents an integrative approach to oral feeding in which rapid technological advances and personalized transcriptomics can safely and noninvasively be brought to the bedside to inform medical care decisions and improve care and outcomes.OBJECTIVE: The study aimed to conduct a multicenter randomized control trial (RCT) to combine molecular and behavioral methods in an experimental conceptualization approach to map the effects of PULSED somatosensory stimulation on salivary gene expression in the context of the acquisition of oral feeding habits in high-risk human neonates. The aims of this study represent the first attempt to combine noninvasive treatment strategies and transcriptomic assessments of high-risk extremely preterm infants (EPI) to (1) improve oral feeding behavior and skills, (2) further our understanding of the gene ontology of biologically diverse pathways related to oral feeding, (3) use gene expression data to personalize neonatal care and individualize treatment strategies and timing interventions, and (4) improve long-term developmental outcomes.METHODS: A total of 180 extremely preterm infants from three neonatal intensive care units (NICUs) will be randomized to receive either PULSED or SHAM (non-pulsing) orocutaneous intervention simultaneous with tube feedings 3 times per day for 4 weeks, beginning at 30 weeks postconceptional age. Infants will also be assessed 3 times per week for NNS performance, and multiple saliva samples will be obtained each week for transcriptomic analysis, until infants have achieved full oral feeding status. At 18 months corrected age (CA), infants will undergo neurodevelopmental follow-up testing, the results of which will be correlated with feeding outcomes in the neo-and post-natal period and with gene expression data and intervention status.RESULTS: The ongoing National Institutes of Health funded randomized controlled trial R01HD086088 is actively recruiting participants. The expected completion date of the study is 2021.CONCLUSIONS: Differential salivary gene expression profiles in response to orosensory entrainment intervention are expected to lead to the development of individualized interventions for the diagnosis and management of oral feeding in preterm infants.TRIAL REGISTRATION: ClinicalTrials.gov NCT02696343; https://clinicaltrials.gov/ct2/show/NCT02696343 (Archived by WebCite athttp://www.webcitation.org/6r5NbJ9Ym).