Abstract: Objective To compare the effect of caffeine citrate and aminophylline on neurological development in preterm infants, in order to provide reference for the early intervention of preterm infants. Methods Totally 62 infants with apnea of prematurity (AOP) treated with caffeine citrate was enrolled as study group from June 2014 to June 2018,and 69 AOP infants treated with aminophylline were selected as control group from December 2011 to May 2014.Brain magnetic resonance image(MRI)scanning was conducted to compare white matter disease(WMD) between caffeine citrate group and aminophylline group at 3 to 8 days after birth and corrected gestational age of 40 weeks.Neurological development was assessed by Gessell Scales of Infant Development in 6 months and 12 months and was compared between the two groups. Results There were no significant differences on sex, gestational age at birth, birth weight, glucocorticoids use before birth and delivery mode, Apgar score at 5 minutes, assisted ventilation, as well as surfactant therapy between caffeine citrate and aminophylline group(P>0.05).Difference on WMD between the two groups was not found at 3 to 8 days after birth(P>0.05), but it was significant at corrected gestational age of 40 weeks(P<0.05).After following up to corrected age of 6 months, the scores of gross motor, fine motor, personal-social contact in caffeine citrate group were significantly higher than those in aminophylline group(P<0.05).And after following up to corrected age of 12 months, the scores of gross motor, fine motor, language and adaptability in caffeine citrate group were significantly higher than those in aminophylline group(P<0.05). Conclusion Caffeine citrate can potentially improve the neurological development outcome of AOP infants at 6 and 12 month old.

Key words: apnea of prematurity, caffeine citrate, aminophylline, white matter disease, neurological development

摘要： 目的 比较枸橼酸咖啡因和氨茶碱对早产儿神经行为发育的影响,为早产儿早期合理干预提供临床依据。方法 选择2014年6月-2018年6月在中国西电集团医院新生儿科住院接受枸橼酸咖啡因治疗的原发性呼吸暂停(AOP)早产儿62例作为研究组;2011 年 12 月-2014年5月同在中国西电集团医院新生儿科住院采用氨茶碱治疗的AOP患儿69例作为对照组。出生3~8 d及矫正胎龄40周时分别行头颅MRI检查,评估脑白质损伤(WMD)并进行两组比较;6个月及12个月时应用Gesell婴幼儿发育量表测试比较两组神经行为发育水平。结果 两组患儿在性别、出生胎龄及体重、产前孕母糖皮质激素应用及分娩方式、5 min Apgar评分、辅助通气和表面活性物质的应用等方面差异均无统计学意义(P>0.05)。首次头颅MRI显示两组患儿WMD差异无统计学意义(P>0.05)。矫正胎龄40周时头颅MRI显示,咖啡因组WMD较氨茶碱组明显改善,差异有统计学意义(P<0.05);且6个月及12个月时Gessell婴幼儿发育量表测试,随访至校正6月龄时,咖啡因组患儿的大运动、精细运动及个人-社交评分均高于氨茶碱组(P<0.05);随访至校正12月龄时,咖啡因组患儿的大运动、精细运动、语言、适应性评分均高于氨茶碱组(P<0.05)。结论 枸橼酸咖啡可明显改善AOP患儿6个月及12个月时的神经行为发育。

关键词: 早产儿呼吸暂停, 枸橼酸咖啡因, 氨茶碱, 脑白质损伤, 神经发育