Division of Newborn Medicine, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts, United States of America.
PLoS One. 2012;7(5):e37870. doi: 10.1371/journal.pone.0037870. Epub 2012 May 21.
The current practice in newborn medicine is to subjectively assess when a premature infant is ready to feed by mouth. When the assessment is inaccurate, the resulting feeding morbidities may be significant, resulting in long-term health consequences and millions of health care dollars annually. We hypothesized that the developmental maturation of hypothalamic regulation of feeding behavior is a predictor of successful oral feeding in the premature infant. To test this hypothesis, we analyzed the gene expression of neuropeptide Y2 receptor (NPY2R), a known hypothalamic regulator of feeding behavior, in neonatal saliva to determine its role as a biomarker in predicting oral feeding success in the neonate.
METHODOLOGY/PRINCIPAL FINDINGS: Salivary samples (n = 116), were prospectively collected from 63 preterm and 13 term neonates (post-conceptual age (PCA) 26 4/7 to 41 4/7 weeks) from five predefined feeding stages. Expression of NPY2R in neonatal saliva was determined by multiplex RT-qPCR amplification. Expression results were retrospectively correlated with feeding status at time of sample collection. Statistical analysis revealed that expression of NPY2R had a 95% positive predictive value for feeding immaturity. NPY2R expression statistically significantly decreased with advancing PCA (Wilcoxon test p value<0.01), and was associated with feeding status (chi square p value = 0.013).
CONCLUSIONS/SIGNIFICANCE: Developmental maturation of hypothalamic regulation of feeding behavior is an essential component of oral feeding success in the newborn. NPY2R expression in neonatal saliva is predictive of an immature feeding pattern. It is a clinically relevant biomarker that may be monitored in saliva to improve clinical care and reduce significant feeding-associated morbidities that affect the premature neonate.
目前,新生儿医学领域的常规做法是通过主观评估来判断早产儿何时可以经口喂养。如果评估不准确,可能会导致严重的喂养并发症,从而对早产儿造成长期的健康影响,并导致每年花费数百万医疗保健费用。我们假设,下丘脑对摄食行为的调节发育成熟度是预测早产儿经口喂养成功的一个指标。为了验证这一假设,我们分析了新生儿唾液中神经肽 Y2 受体(NPY2R)的基因表达,NPY2R 是一种已知的下丘脑摄食行为调节因子,以确定其作为生物标志物在预测新生儿经口喂养成功中的作用。
方法/主要发现:我们前瞻性地收集了 63 名早产儿和 13 名足月儿(从受孕后 26 4/7 周到 41 4/7 周)的唾液样本(n=116),并将其分为 5 个预先定义的喂养阶段。通过多重 RT-qPCR 扩增法测定新生儿唾液中的 NPY2R 表达。将表达结果与样本采集时的喂养状态进行回顾性相关性分析。统计分析显示,NPY2R 表达对喂养不成熟有 95%的阳性预测值。随着胎龄的增加,NPY2R 的表达呈统计学显著下降(Wilcoxon 检验 p 值<0.01),并且与喂养状态相关(卡方检验 p 值=0.013)。
结论/意义:下丘脑对摄食行为的调节发育成熟是新生儿经口喂养成功的一个重要组成部分。新生儿唾液中 NPY2R 的表达可以预测不成熟的喂养模式。它是一种具有临床相关性的生物标志物,可通过监测唾液来改善临床护理,减少影响早产儿的严重喂养相关并发症。