重组人促红细胞生成素对早产儿脑损伤保护作用的分析

Protective effects of recombinant human erythropoietin on brain injury in preterm infants

目的探讨重组人促红细胞生成素（rh EPO）对早产儿脑组织的保护作用及其对早产儿纠正年龄1岁内智能发育的影响。方法选择2013年12月至2014年12月广州市妇女儿童医疗中心珠江新城院区新生儿病房收治的出生胎龄〈34周早产儿为研究对象。其中,经患儿家属知情同意后于住院期间使用rh EPO治疗（生后7天开始,250 IU/kg,皮下注射,每周3次）的治愈出院早产儿101例为促红细胞生成素（EPO）组;患儿家属不同意住院期间使用rh EPO治疗的治愈出院早产儿93例为对照组。比较两组患儿42天时的脑干诱发电位（BAEP）及纠正年龄3~6月龄、9~12月龄时的智能发育情况。结果 1EPO组42例和对照组37例患儿BAEP检查报告进行分析：对照组左耳Ⅲ波、Ⅴ波波峰潜伏期（PL）均明显长于EPO组（t值分别为-2.350、-2.357,均P〈0.05）;对照组右耳Ⅰ波、Ⅲ波、Ⅴ波PL均明显长于EPO组（t值分别为-8.494、-2.063、-2.179,均P〈0.05）;对照组左耳Ⅰ~Ⅲ波、Ⅰ~Ⅴ波波峰间潜伏期（IPL）均明显长于EPO组（t值分别为-2.851、-2.634,均P〈0.05）;2对早产儿纠正年龄3~6月龄时进行Gesell测试：EPO组80例,对照组71例,EPO组大运动、精细运动、语言、个人社交发育商均高于对照组,差异均具有统计学意义（t值分别为-2.658、-5.292、-2.311、-4.169,均P〈0.05）;早产儿纠正年龄9~12个月时参加Gesell测试的早产儿为：EPO组72例,对照组59例,EPO组大运动、语言、适应性、个人社交发育商均高于对照组,差异均具有统计学意义（t值分别为-2.082、-2.355、-2.065、-2.385,均P〈0.05）;3EPO组支气管肺发育不良、颅内出血、BAEP异常发生率明显低于对照组,差异均具有统计学意义（χ2值分别为6.686、4.628、4.366,均P〈0.05）。结论出生胎龄〈34周早产儿生后7天开始使用rh EPO治疗可以降低住院期间支气管肺发育不良、颅内出血及脑干听觉诱发电位异常的发生率,有利于促进早产儿纠正胎龄1岁内的智能发育。

Objective To explore the protective effect of recombinant human erythropoietin （rhEPO） on the brain tissue and its effects on improving the intelligence development of preterm infants under corrected age of 1 year. Methods Preterm infants whose gestational ages were less than 34 weeks were selected as research objects. All these infants were hospitalized in Zhujiang New Town Branch of Guangdong Women and Children＇ s Medical Center during the period of December 2013 to December 2014. With informed consent from family members, 101 cases of recovered preterm infants treated with rhEPO during their hospital stays were included in EPO group. The treatment started at the 7th day after birth （250 IU/kg through subcutaneous injection; three times a week）. As for another 93 cases of recovered infants, whose patients disapproved of using rhEPO during their hospital stays were chosen in control group. Infants＇ brainstem auditory evoked potentials （BAEP） at the 42nd day after birth and their state of intelligence development at 3 -6 months or 9 - 12 months corrected age were compared between two groups. Results BAEP examination reports of 42 infants in EPO group and 37 cases in the control group were analyzed. Peak latency （PL） of wave m and Vof the left ear in the control group was longer than that in EPO group （t value was - 2.350 and - 2. 357, respectively, both P 〈 0.05 ）. The PL of wave I , m and V of the right ear in the control group was significantly longer than that in EPO group （ t value was - 8. 494, - 2. 063, and - 2. 179, respectively, all P 〈 0.05 ）. The inter peak latency （IPL） of wave I - HI and wave I - Vof the left ear in the control group was significantly longer than that in EPO group （t value was -2. 851 and -2. 634, respectively, both P 〈 0.05）. In total, 80 cases of preterm infants from EPO group and 71 cases from the control group underwent Gesell test at the corrected age of 3 -6 months. Infants from EPO group exceeded the control group in gross motor, fine motor, language, adaptability, and individual＇s developmental quotient. The preceding differences were of statistical significance （t value was - 2. 658, - 5. 292, - 2.311 and -4. 169, respectively, all P 〈 0.05 ）. Besides, 72 cases of preterm infants from EPO group and 59 cases from the control group underwent Gesell test at the corrected age of 9 - 12 months. Infants from EPO group had higher scores in gross motor, language, adaptability, and individual＇s developmental quotient than those in the control group, and the differences were of statistical significance （t value was - 2. 082, - 2. 355, - 2. 065 and - 2. 385, respectively, all P 〈 0.05）. The incidence rate of bronchopulmonary dysplasia, intraeranial hemorrhage and abnormal BAEP was significantly lower in EPO group than in the control group with significant difference （X2 value was 6. 686, 4. 628 and 4. 366, respectively, all P 〈 0. 05 ）. Conclusion The incidence rate of bronchopulmonary dysplasia, intracranial hemorrhage and abnormal BAEP can be lowered if preterm infants at the gestational age of less than 34 weeks begin to take rhEPO 7 days after birth. Besides, rhEPO is beneficial to the intelligence development of preterm infants at the corrected gestational age of less than 1 year.