Maron Jill L, Hwang Jooyeon S, Pathak Subash, Ruthazer Robin, Russell Ruby L, Alterovitz Gil
Division of Newborn Medicine, Mother Infant Research Institute at Tufts Medical Center, Floating Hospital for Children at Tufts Medical Center, Boston, MA.
Division of Newborn Medicine, Mother Infant Research Institute at Tufts Medical Center, Floating Hospital for Children at Tufts Medical Center, Boston, MA.
J Pediatr. 2015 Feb;166(2):282-8.e5. doi: 10.1016/j.jpeds.2014.10.065.
To combine mathematical modeling of salivary gene expression microarray data and systems biology annotation with reverse-transcription quantitative polymerase chain reaction amplification to identify (phase I) and validate (phase II) salivary biomarker analysis for the prediction of oral feeding readiness in preterm infants.
Comparative whole-transcriptome microarray analysis from 12 preterm newborns pre- and postoral feeding success was used for computational modeling and systems biology analysis to identify potential salivary transcripts associated with oral feeding success (phase I). Selected gene expression biomarkers (15 from computational modeling; 6 evidence-based; and 3 reference) were evaluated by reverse-transcription quantitative polymerase chain reaction amplification on 400 salivary samples from successful (n = 200) and unsuccessful (n = 200) oral feeders (phase II). Genes, alone and in combination, were evaluated by a multivariate analysis controlling for sex and postconceptional age (PCA) to determine the probability that newborns achieved successful oral feeding.
Advancing PCA (P < .001) and female sex (P = .05) positively predicted an infant's ability to feed orally. A combination of 5 genes, neuropeptide Y2 receptor (hunger signaling), adneosine-monophosphate-activated protein kinase (energy homeostasis), plexin A1 (olfactory neurogenesis), nephronophthisis 4 (visual behavior), and wingless-type MMTV integration site family, member 3 (facial development), in addition to PCA and sex, demonstrated good accuracy for determining feeding success (area under the receiver operator characteristic curve = 0.78).
We have identified objective and biologically relevant salivary biomarkers that noninvasively assess a newborn's developing brain, sensory, and facial development as they relate to oral feeding success. Understanding the mechanisms that underlie the development of oral feeding readiness through translational and computational methods may improve clinical decision making while decreasing morbidities and health care costs.
将唾液基因表达微阵列数据的数学建模和系统生物学注释与逆转录定量聚合酶链反应扩增相结合，以识别（I期）并验证（II期）唾液生物标志物分析，用于预测早产儿经口喂养的准备情况。
对12例早产儿经口喂养成功前后进行全转录组微阵列比较分析，用于计算建模和系统生物学分析，以识别与经口喂养成功相关的潜在唾液转录本（I期）。通过逆转录定量聚合酶链反应扩增，对400份来自经口喂养成功（n = 200）和不成功（n = 200）的婴儿的唾液样本，评估选定的基因表达生物标志物（15个来自计算建模；6个基于证据；3个为参考）（II期）。通过控制性别和孕龄（PCA）的多变量分析，对单个基因和基因组合进行评估，以确定新生儿经口喂养成功的概率。
孕龄增加（P < .001）和女性（P = .05）对婴儿经口喂养能力有正向预测作用。除PCA和性别外，神经肽Y2受体（饥饿信号）、腺苷单磷酸活化蛋白激酶（能量稳态）、丛蛋白A1（嗅觉神经发生）、肾结核4（视觉行为）和无翅型MMTV整合位点家族成员3（面部发育）这5个基因的组合，在确定喂养成功方面显示出良好的准确性（受试者操作特征曲线下面积 = 0.78）。
我们已经确定了客观且具有生物学相关性的唾液生物标志物，这些标志物可以无创地评估新生儿与经口喂养成功相关的大脑、感觉和面部发育情况。通过转化和计算方法了解经口喂养准备情况发展的潜在机制，可能会改善临床决策，同时降低发病率和医疗保健成本。
