1 MR Research Centre, Children's University Hospital of Zurich, Switzerland.
2 Department of Neonatology, University Hospital of Zurich, Switzerland.
Brain. 2015 Feb;138(Pt 2):388-97. doi: 10.1093/brain/awu363. Epub 2014 Dec 22.
Despite improved survival, many preterm infants undergo subsequent neurodevelopmental impairment. To date, no neuroprotective therapies have been implemented into clinical practice. Erythropoietin, a haematopoietic cytokine used for treatment of anaemia of prematurity, has been shown to have neuroprotective and neuroregenerative effects on the brain in many experimental studies. The aim of the study was to assess the effect of recombinant human erythropoietin on the microstructural development of the cerebral white matter using tract-based spatial statistics performed at term equivalent age. A randomized, double-blind placebo-controlled, prospective multicentre study applying recombinant human erythropoietin in the first 42 h after preterm birth entitled 'Does erythropoietin improve outcome in preterm infant' was conducted in Switzerland (NCT00413946). Preterm infants were given recombinant human erythropoietin (3000 IU) or an equivalent volume of placebo (NaCl 0.9%) intravenously before 3 h of age after birth, at 12-18 h and at 36-42 h after birth. High resolution diffusion tensor imaging was obtained at 3 T in 58 preterm infants with mean (standard deviation) gestational age at birth 29.75 (1.44) weeks, and at scanning at 41.1 (2.09) weeks. Imaging was performed at a single centre. Voxel-wise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics to test for differences in fractional anisotropy between infants treated with recombinant human erythropoietin and placebo using a general linear model, covarying for the gestational age at birth and the corrected gestational age at the time of the scan. Preterm infants treated with recombinant human erythropoietin demonstrated increased fractional anisotropy in the genu and splenium of the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterally. Mean fractional anisotropy was significantly higher in preterm infants treated with recombinant human erythropoietin than in those treated with placebo (P < 0.001). We conclude that early recombinant human erythropoietin administration improves white matter development in preterm infants assessed by diffusion tensor imaging and tract-based spatial statistics.
尽管早产儿的存活率有所提高，但许多早产儿仍会出现神经发育障碍。迄今为止，尚无神经保护疗法应用于临床实践。促红细胞生成素是一种用于治疗早产儿贫血的造血细胞因子，许多实验研究表明其对大脑具有神经保护和神经再生作用。本研究旨在通过在足月龄时进行基于束的空间统计学评估重组人促红细胞生成素对脑白质微观结构发育的影响。一项在瑞士进行的、题为“促红细胞生成素是否能改善早产儿预后”的、应用于早产儿出生后 42 小时内的重组人促红细胞生成素的随机、双盲、安慰剂对照、前瞻性多中心研究（NCT00413946），纳入了早产儿，并给予重组人促红细胞生成素（3000IU）或等量的安慰剂（0.9%NaCl）静脉注射。早产儿在出生后 3 小时内、12-18 小时和 36-42 小时内接受治疗。在 58 例平均（标准差）胎龄为 29.75（1.44）周的早产儿中进行了高分辨率弥散张量成像，在扫描时的胎龄为 41.1（2.09）周，在 3T 磁共振扫描仪上进行。成像在单一中心进行。使用基于束的空间统计学方法对各向异性分数数据进行体素水平的统计分析，以一般线性模型检验接受重组人促红细胞生成素和安慰剂治疗的婴儿之间各向异性分数的差异，模型中协变量包括出生时的胎龄和扫描时的校正胎龄。与接受安慰剂治疗的早产儿相比，接受重组人促红细胞生成素治疗的早产儿的胼胝体膝部和压部、内囊前肢和后肢以及皮质脊髓束双侧的各向异性分数增加。接受重组人促红细胞生成素治疗的早产儿的平均各向异性分数明显高于接受安慰剂治疗的早产儿（P<0.001）。我们的结论是，早期应用重组人促红细胞生成素可改善通过弥散张量成像和基于束的空间统计学评估的早产儿的白质发育。
