Barlow Steven Michael, Maron Jill Lamanna, Alterovitz Gil, Song Dongli, Wilson Bernard Joseph, Jegatheesan Priya, Govindaswami Balaji, Lee Jaehoon, Rosner Austin Oder
Center for Brain, Biology, and Behavior, Department of Special Education and Communication Disorders, Biological Systems Engineering, University of Nebraska, Lincoln, NE, United States.
Tufts Medical Center, Division of Neonatology, Department of Pediatrics, Boston, MA, United States.
JMIR Res Protoc. 2017 Jun 14;6(6):e113. doi: 10.2196/resprot.7712.
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.
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.
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.
The ongoing National Institutes of Health funded randomized controlled trial R01HD086088 is actively recruiting participants. The expected completion date of the study is 2021.
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.
ClinicalTrials.gov NCT02696343; https://clinicaltrials.gov/ct2/show/NCT02696343 (Archived by WebCite at http://www.webcitation.org/6r5NbJ9Ym).
尽管在高危早产儿护理方面取得了众多医学进展，但经口喂养仍是这一脆弱群体面临的首要且最具挑战性的神经学难题之一。为改善喂养及发育结局，迫切需要客观、定量且无创的评估工具以及神经治疗策略。已证实，脉冲式气动口周刺激可改善存在延迟或紊乱的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识别与成功的新生儿经口喂养行为直接相关的生物标志物。无创治疗策略与转录组分析相结合代表了一种经口喂养的综合方法，借助快速的技术进步和个性化转录组学，可安全无创地应用于床边，为医疗决策提供依据，改善护理及结局。
本研究旨在开展一项多中心随机对照试验（RCT），以实验性概念化方法结合分子与行为学方法，探究脉冲体感刺激对高危人类新生儿在养成经口喂养习惯过程中唾液基因表达的影响。本研究的目的代表了首次尝试将无创治疗策略与高危极早产儿（EPI）的转录组评估相结合，以（1）改善经口喂养行为和技能，（2）加深我们对与经口喂养相关的生物多样性途径的基因本体论的理解，（3）利用基因表达数据实现新生儿护理个性化并使治疗策略和定时干预个体化，以及（4）改善长期发育结局。
来自三个新生儿重症监护病房（NICU）的总共180名极早产儿将被随机分组，从孕龄30周开始，每天接受3次脉冲式或假（非脉冲式）口周干预，同时进行管饲，持续4周。每周还将对婴儿的NNS表现进行3次评估，每周获取多个唾液样本进行转录组分析，直至婴儿达到完全经口喂养状态。在矫正年龄（CA）18个月时，婴儿将接受神经发育随访测试，其结果将与新生儿期和产后的喂养结局以及基因表达数据和干预状态相关联。
正在进行的由美国国立卫生研究院资助的随机对照试验R01HD086088正在积极招募参与者。该研究预计完成日期为2021年。
预计对口感觉夹带干预的不同唾液基因表达谱将有助于开发针对早产儿经口喂养诊断和管理的个性化干预措施。
ClinicalTrials.gov NCT02696343；https://clinicaltrials.gov/ct2/show/NCT02696343（由WebCite存档于http://www.webcitation.org/6r5NbJ9Ym）。
