小剂量氨茶碱对早产儿脑神经发育的影响

Neurodevelopment effect of low dose aminophylline treated with prematurity

目的探讨小剂量氨茶碱对早产儿临床预后及脑神经发育的影响。方法选择2007年12月至2009年12月本院新生儿重症监护病房收治的日龄<14天、因呼吸暂停或便于撤离机械通气用氨茶碱治疗的极低出生体重早产儿,对于机械通气者与未机械通气治疗者进行分层分析。将机械通气患儿随机分为观察1组、观察2组和对照组,观察1组于撤机前应用氨茶碱,持续至无呼吸暂停后5天;观察2组于机械通气第1天开始应用氨茶碱,持续至校正胎龄32周;对照组不用氨茶碱。有呼吸暂停而不需机械通气者为无机械通气组,应用氨茶碱的患儿为观察组,未用氨茶碱的患儿为对照组。氨茶碱首剂4mg/kg,维持量2mg/kg,每12h一次。观察并记录住院时间、上呼吸机时间、支气管肺发育不良(BPD)、早产儿视网膜病(ROP)、脑白质软化(PVL)、坏死性小肠结肠炎(NEC)、动脉导管未闭(PDA)发生率及预后,所有生存早产儿出院后进行听力、视力、体格智力发育随访。结果 353例研究对象入选,其中6例在治疗中放弃,7例死亡(4例住院期间,3例出院后婴幼儿期死亡)。住院治疗期间,无机械通气患儿观察组住院时间短于对照组[(39.4±15.7)天比(45.2±12.1)天,P<0.05],BPD、PVL的发生率低于对照组[1.3%比9.0%,1.3%比10.3%,P<0.05];机械通气组中,观察2组与观察1组住院时间、上呼吸机治疗时间均短于对照组[(40.3±13.5)、(47.4±14.7)天比(52.3±17.6)天,(3.9±3.2)、(5.1±3.9)天比(5.9±4.3)天,P<0.05],BPD、PVL、NEC的发生率低于对照组[3.1%、9.1%比10.0%,3.1%、4.5%比10.0%,3.1%、4.5%比13.8%,P<0.05],尤其以观察2组明显。随访过程中,各组均有患儿失访,无机械通气患儿失访60例,机械通气患儿失访54例,完成随访者进行比较,无机械通气患儿脑瘫、耳聋、失明的发生率观察组与对照组比较差异无统计学意义(P>0.05),需要早期干预的患儿明显少于对照组(P<0.05)。机械通气组患儿脑瘫、耳聋、失明的发生率观察组与对照组比较差异无统计学意义(P>0.05),MDI<70、需要早期干预或进行语言训练的患儿明显减少(P<0.05)。结论应用氨茶碱治疗早产儿呼吸暂停或便于撤离呼吸机,对患儿临床预后及脑神经发育有一定改善,无明显不良反应及后遗症的发生。

Objective To study the effect of small-dose aminophylline for apnea of prematurity and to evaluate the neurodevelopment of preterm infants treated with aminophylline. Methods Very-low- birth-weight （VLBW） infants admitted to NICU from December 2007 to December 2009 were studied. Their ages were below 14 days, and they were treated with aminophylline for apnea or weaning from mechanical ventilation. Comparisons were made between infants receiving ventilation （vent group）and those without（ unvent group）. The vent group were further assigned into 3 groups randomly ：group 1 were treated with aminophylline beginning from removal of endotracheal tube to 5 days after the disappearance of apnea, group 2 were treated with aminophylline from the first day of ventilation to 32 weeks of corrected gestational age, the control group received no aminophylline treatment. The unvent group showed apnea but had no ventilation. Intravenous aminophylline loading dose was 4mg/kg, and maintenance dose was 2 mg/kg every 12 hours. The primary outcomes included duration of hospitalization, duration of ventilation, bronchopulmonary dysplasia （ BPD）, periventricular leucomalacia （PVL）, necrotizing enterocolitise （NEC）, parent ductus arteriosus （PDA） and death. The second outcome were neural development assessed at 18 months of age. Results 353 neonates were studied, 6 neonates were abandoned during the treatment, 7 neonates demised （4 during hospital stay, and 3 after discharge）. The duration of hospitalization was shorter in the unvent group than the control group [ （39. 4 ± 15.7 ） vs. （45.2 ± 12. 1 ） days, P 〈 0. 05 ], and the incidence of BPD, CLD was statistically significantly lower in the unvent group [ l. 3% vs. 9.0% , 1.3% vs. 10.3% , P 〈 0. 05 ]. For the vent group, the duration of hospitalization and ventilation were shorter in both group 1 and group 2 than in control group [ （40. 3 ± 13.5 ）, （47.4 ± 14. 7 ） days vs. （ 52.3 ± 17.6 ） days, （ 3.9 -± 3.2 ）, （ 5.1 ± 3.9 ） days vs. （5.9 ± 4. 3 ）days,P 〈 0. 05 ], and the incidence of BPD, PVL, NEC was lower in both group 1 and group 2 [3.1%,9.1% vs. 10.0%; 3.1%, 4.5% vs. 10.0%; 3.1%, 4.5% vs. 13.8%, P 〈 0.05 ]. During follow up, 60 cases were lost in the vent group, and 54 cases in the unvent group. For neonates without ventilation, the incidence of cerebral palsy, severe visual loss showed no significant difference between control group and treatment group. But the need for early invention was less in unvent group than control group. As for vent group, the incidence of cerebral palsy, severe visual loss showed no significant difference between control group and treatment group, but the need of early intervention, speech therapy and the rate of MDI 〈 70 were lower in group 1 and 2 （ P 〈 0. 05 ）. Conclusion For preterm infants treated with aminophylline, the clinical and neurodevelopment prognosis were improved, and there were no serious side effects or complications occurred.