Murphy B P, Inder T E, Huppi P S, Warfield S, Zientara G P, Kikinis R, Jolesz F A, Volpe J J
Division of Newborn Medicine, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA.
Pediatrics. 2001 Feb;107(2):217-21. doi: 10.1542/peds.107.2.217.
The specific aim of this study was to quantify at term the influence of postnatal systemic dexamethasone treatment for neonatal chronic lung disease on subsequent brain growth and development in premature infants without evidence of severe intraventricular hemorrhage or white matter injury.
Eighteen premature (23 to 31 weeks) infants, 7 treated with dexamethasone and 11 not treated, were studied at term, ie, 38 to 41 postconceptional weeks, by an advanced quantitative volumetric 3-dimensional magnetic resonance imaging (MRI) technique to quantify cerebral tissue volumes. Fourteen healthy term infants also were studied for comparison. A sequence of image processing algorithms was used to segment each of the MRI slices into the following separate tissue classes: cerebral cortical gray matter, basal ganglia/thalami, unmyelinated white matter, myelinated white matter, and cerebrospinal fluid, all classified based on magnetic resonance signal intensity and anatomic location. A final summing of voxels for each tissue class was performed to compute absolute volumes in milliliters.
Cerebral cortical gray matter volume in premature infants treated with dexamethasone was reduced 35% when compared with gray matter volume in premature infants not treated with dexamethasone (mean +/- standard deviation, 130.3 +/- 54.0 vs 200.6 +/- 35.1 mL, respectively). Subcortical gray matter volumes (basal ganglia and thalami) and myelinated and unmyelinated white matter volumes were not significantly different among the treated and untreated groups. However, premature infants treated with dexamethasone exhibited a reduction (30%) in total cerebral tissue volume compared with total cerebral tissue volume in both the premature infants not treated with dexamethasone and the control term infants (312.7 +/- 43.7 vs 448.2 +/- 50.2 and 471.6 +/- 36.4 mL respectively). This latter finding relates primarily to the decrease in cerebral cortical gray matter volume.
The data suggest an impairment in brain growth, principally affecting cerebral cortical gray matter, secondary to systemic dexamethasone therapy. Although the premature infants who received dexamethasone were smaller with more severe respiratory disease, these findings are consistent with growing evidence of a potential deleterious effect of dexamethasone on neonatal brain and subsequent neurodevelopmental outcome. This apparent deleterious effect should be taken into consideration by clinicians when weighing the potential risks and benefits of this therapy for low birth weight infants with neonatal chronic lung disease.
本研究的具体目的是，在足月时量化出生后全身应用地塞米松治疗新生儿慢性肺病对无严重脑室内出血或白质损伤证据的早产儿后续脑生长和发育的影响。
18名早产儿（23至31周），其中7名接受地塞米松治疗，11名未接受治疗，在足月时，即孕龄38至41周时，采用先进的定量容积三维磁共振成像（MRI）技术对脑组织体积进行量化研究。还研究了14名健康足月儿作为对照。使用一系列图像处理算法将每个MRI切片分割为以下不同的组织类别：大脑皮质灰质、基底神经节/丘脑、未髓鞘化白质、髓鞘化白质和脑脊液，所有这些均根据磁共振信号强度和解剖位置进行分类。对每个组织类别的体素进行最终求和，以计算以毫升为单位的绝对体积。
与未接受地塞米松治疗的早产儿相比，接受地塞米松治疗的早产儿的大脑皮质灰质体积减少了35%（平均±标准差，分别为130.3±54.0和200.6±35.1 mL）。治疗组和未治疗组的皮质下灰质体积（基底神经节和丘脑）以及髓鞘化和未髓鞘化白质体积无显著差异。然而，与未接受地塞米松治疗的早产儿和足月对照婴儿相比，接受地塞米松治疗的早产儿脑组织总体积减少了30%（分别为312.7±43.7、448.2±50.2和471.6±36.4 mL）。后一发现主要与大脑皮质灰质体积的减少有关。
数据表明，全身应用地塞米松治疗会损害脑生长，主要影响大脑皮质灰质。尽管接受地塞米松治疗的早产儿体型较小且患有更严重的呼吸系统疾病，但这些发现与越来越多的证据一致，即地塞米松对新生儿脑和后续神经发育结局可能存在有害影响。临床医生在权衡这种疗法对患有新生儿慢性肺病的低体重婴儿的潜在风险和益处时，应考虑到这种明显的有害影响。
