Procedural Pain and Brain Development in Premature Newborns
Procedural Pain and Brain Development in Premature Newborns
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DOI：
10.1002/ana.22267
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发表时间：
2012-03-01
影响因子：
11.2
通讯作者：
Miller, Steven P.
中科院分区：
文献类型：
--
作者：
Brummelte, Susanne;Grunau, Ruth E.;Miller, Steven P.
目的：早产儿在大脑快速发育期间，在新生儿重症监护室（NICU）中暴露于多种痛苦的程序。我们的目的是研究新生儿重症监护室（NICU）的手术疼痛与极早产儿早期脑发育之间的关系。（N = 86;胎龄24-32周）从出生起前瞻性随访，并采用磁共振成像、三维磁共振波谱成像和扩散张量成像进行研究：在生命早期（中位数，32.1周）扫描1次，在足月年龄（中位数，40周）扫描2次。我们计算了N-乙酰天冬氨酸胆碱比（NAA/胆碱），乳酸胆碱比，平均扩散率，和白色物质分数各向异性（FA）从多达7个白色和4个皮层下灰质区的利益。手术疼痛被量化为从出生到足月或扫描2的皮肤破裂事件的数量。使用广义估计方程模型对数据进行分析，调整临床混杂因素，如疾病严重程度、吗啡暴露、脑损伤和手术。在综合调整多个临床因素后，新生儿手术疼痛增加与白色FA减少相关（β =-0.0002，p = 0.028）和皮质下灰质NAA/胆碱减少（β =-0.0006，p = 0.004）。减少FA预测早期疼痛（扫描前1），而较低的NAA/胆碱预测整个新生儿过程中的疼痛暴露，这表明一个主要的和早期的影响与继发性白色物质的变化对皮质下结构。解释：早期程序性疼痛极早产儿可能有助于受损的大脑发育。神经网络2012;71：385-396
Objective: Preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU) during a period of rapid brain development. Our aim was to examine relationships between procedural pain in the NICU and early brain development in very preterm infants.Methods: Infants born very preterm (N = 86; 24-32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery.Results: After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (beta = -0.0002, p = 0.028) and reduced subcortical gray matter NAA/choline (beta = -0.0006, p = 0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes.Interpretation: Early procedural pain in very preterm infants may contribute to impaired brain development. ANN NEUROL 2012;71:385-396