Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease
Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease
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DOI：
10.1542/peds.2004-1275
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发表时间：
2005-07-01
期刊：
影响因子：
8
通讯作者：
Huppi, PS
中科院分区：
文献类型：
--
作者：
Lodygensky, GA;Rademaker, K;Huppi, PS
目标。新生儿糖皮质激素治疗慢性肺部疾病后潜在的神经发育障碍备受关注。地塞米松是这种临床环境中最常用的皮质类固醇，已被证明会损害早产儿的皮质发育。本研究利用三维MRI结合先进的图像处理和神经认知评估技术，评估早产儿本身和新生儿氢化可的松治疗对脑结构和功能发育的长期影响。对60名早产儿，包括25名接受氢化可的松治疗的儿童和35名未接受氢化可的松治疗的儿童和21名足月出生的儿童进行了定量核磁共振成像和神经认知评估(韦氏儿童智力量表修订[WISC-R])的评估，平均年龄8岁。用自动图像分割技术确定大脑灰质、白质和脑脊液的组织体积。此外，还手动测定了海马体的体积。WISC-R评分被记录为评估时的平均智力分数。新生儿氢化可的松治疗慢性肺部疾病的起始剂量为每天5毫克/公斤，逐渐减少，至少持续3周。与足月儿(早产儿：649±/-4.4毫升；足月儿：666±/-7.3毫升)相比，早产儿(不考虑氢化可的松治疗)的大脑灰质体积减少。在早产儿组中，出生体重与8岁时灰质体积相关(r=0.421)。早产儿的脑脊液容量高于足月儿(早产儿：228±/-4.9毫升；足月儿：206±/-8.2毫升)。早产儿海马区总体积较小，男童(早产儿：6.1+/-0.13毫升；足月儿：6.56+/-0.2毫升)海马区体积缩小更明显。早产儿的韦氏智力量表得分低于足月儿(早产儿：99.4+/-12.4；足月儿：109.6+/-8.8)。与未治疗的婴儿相比，接受氢化可的松治疗的早产儿在灰质(氢化可的松治疗的早产儿：650±/-7.0mL；不使用氢化可的松的早产：640±/-5.6mL)、白质(使用氢化可的松的早产：503+/-6.1mL；不使用氢化可的松的早产：510+/-4.9mL)和脑脊液(使用氢化可的松的早产：227+/-7.4mL；不使用氢化可的松的早产：224±/-6.0mL)的体积非常相似。两组大鼠海马区体积相似(早产儿使用氢化可的松：5.92±0.15毫升；未使用氢化可的松的早产儿：5.81±0.12毫升)。WISC-R评分两组均在正常范围内，两组间差异无统计学意义(早产儿应用氢化可的松：100.8+/-13；未应用氢化可的松的早产：98.6+/-12.3)。早产儿与轻微的大脑结构差异有关，这种差异在8岁时持续存在，并伴随着神经认知评估中的较低分数。这些数据表明，围产期给予所述剂量的氢化可的松对神经结构大脑发育或神经认知结果都没有长期影响。
Objective. There is much concern about potential neurodevelopmental impairment after neonatal corticosteroid treatment for chronic lung disease. Dexamethasone is the corticosteroid most often used in this clinical setting, and it has been shown to impair cortical growth among preterm infants. This study evaluated long-term effects of prematurity itself and of neonatal hydrocortisone treatment on structural and functional brain development using three-dimensional MRI with advanced image-processing and neurocognitive assessments.Methods. Sixty children born preterm, including 25 children treated with hydrocortisone and 35 children not treated with hydrocortisone, and 21 children born at term were evaluated, at a mean age of 8 years, with quantitative MRI and neurocognitive assessments (Wechsler Intelligence Scales for Children-Revised [WISC- R]). Automatic image segmentation was used to determine the tissue volumes of cerebral gray matter, white matter, and cerebrospinal fluid. In addition, the volume of the hippocampus was determined manually. WISC- R scores were recorded as mean intelligence scores at evaluation. Neonatal hydrocortisone treatment for chronic lung disease consisted of a starting dose of 5 mg/ kg per day tapered over a minimum of 3 weeks.Results. Cerebral gray matter volume was reduced among preterm children (regardless of hydrocortisone treatment), compared with children born at term (preterm: 649 +/- 4.4 mL; term: 666 +/- 7.3 mL). Birth weight was shown to correlate with gray matter volume at 8 years of age in the preterm group (r = 0.421). Cerebrospinal fluid volume was increased among children born preterm, compared with children born at term (preterm: 228 +/- 4.9 mL; term: 206 +/- 8.2 mL). Total hippocampal volume tended to be lower among children born preterm, with a more pronounced reduction of hippocampal volume among boys ( preterm: 6.1 +/- 0.13 mL; term: 6.56 +/- 0.2 mL). The WISC- R score was lower for children born preterm, compared with children born at term (preterm: 99.4 +/- 12.4; term: 109.6 +/- 8.8). Children treated with neonatal hydrocortisone had very similar volumes of gray matter (preterm with hydrocortisone: 650 +/- 7.0 mL; preterm without hydrocortisone: 640 +/- 5.6 mL), white matter (preterm with hydrocortisone: 503 +/- 6.1 mL; preterm without hydrocortisone: 510 +/- 4.9 mL), and cerebrospinal fluid ( preterm with hydrocortisone: 227 +/- 7.4 mL; preterm without hydrocortisone: 224 +/- 6.0 mL), compared with untreated infants. The hippocampal volumes were similar in the 2 groups (preterm with hydrocortisone: 5.92 +/- 0.15 mL; preterm without hydrocortisone: 5.81 +/- 0.12 mL). The WISC- R score assessments were within the normal range for both groups, with no difference between the groups (preterm with hydrocortisone: 100.8 +/- 13; preterm without hydrocortisone: 98.6 +/- 12.3).Conclusions. Prematurity is associated with mild brain structural differences that persist at 8 years of age, with associated lower scores in neurocognitive assessments. The data suggest that perinatal hydrocortisone given at the described dosage has no long- term effects on either neurostructural brain development or neurocognitive outcomes.