更昔洛韦治疗先天性巨细胞病毒感染患儿的系统评价

目的：评价更昔洛韦（GCV）治疗先天性巨细胞病毒（CMV）感染的疗效及安全性。 方法：计算机检索PubMed（1988.1～2009.1）、EMbase（1988.1～2009.1）、Cochrane图书馆（2003年第3期和2009年第1期）、中国学术期刊全文数据库（1994.1～2009.1）、中国生物医学文献数据库（1994.1～2009.1）、中文生物医学期刊文献数据库（1994.1～2009.1）,纳入用GCV治疗及未用GCV治疗先天性CMV感染的随机及半随机对照试验。对研究人群的干预措施及结果：进行分析评价及meta分析。结果共纳入10篇文献。meta分析结果表明,GCV治疗后在先天性CMV感染患儿的病情好转率（91.4%vs 34.0%,P＜0.01）及病毒感染指标转阴率（87.6%vs 15.3%,P＜0.01）这两方面均明显高于未治疗的对照组。GCV治疗后还可明显降低CMV感染患者的听力障碍发生率（4.7% vs 37.2%,P＜0.01）。GCV治疗组的不良反应发生率低。结论：本系统评价提示,对先天性CMV感染的婴儿,使用GCV治疗可以增加患儿的治疗好转率,增加CMV感染指标的转阴率,减少听力障碍的发生率,而GCV的不良反应发生率低。但因纳入研究的总样本量较小,证据强度有限,需更多高质量研究证实。［中国当代儿科杂志,2010,12（1）：35-39］     

新生儿先天性巨细胞病毒感染的临床研究

目的探讨新生儿先天性巨细胞病毒（CMV）感染的临床特征以及更昔洛韦治疗的临床疗效及其对预后的影响。方法先天性CMV感染新生儿73例分为试验组（n=32）、对照组（n=41）。二组患儿均给予茵栀黄退黄、蓝光照射、丙种球蛋白等对症支持治疗。试验组加用更昔洛韦[7.5mg/（kg.次）]治疗;对照组未使用更昔洛韦。观察更昔洛韦的临床疗效,并比较二组转归情况。结果1.临床特征：73例患儿均有症状性感染,以全身性感染为主（80.8%）;消化系统受累最常见（95.89%）,病理性黄疸是其主要首发症状和主要临床表现（95.89%）;病程中可并其他病原微生物感染,以机会菌败血症最常见（14.1%）;出生缺陷发生率为6.4%。2.临床疗效：试验组治疗后临床表现、辅助检查、病原学检查阴转率与对照组比较均有显著性差异（Pa〈0.001,0.005）。3.转归：试验组痊愈26例（81.3%）,显效6例（18.7%）;对照组进步14例（34.1%）,未愈27例（65.9%）,二组临床疗效比较有显著性差异（P〈0.005）。结论新生儿先天性CMV感染主要表现为有症状性全身性感染,及时予更昔洛韦正规治疗,能明显改善预后。     

更昔洛韦（丽科伟）在先天性巨细胞病毒感染的临床应用

目的：评价更昔洛韦治疗先天性巨细胞病毒（CMV）感染的疗效及其影响因素。方法：将30例确诊为先天性CMV感染的患儿分为症状性16例和无症状性14例两组，按照丙昔洛韦诱导和维持治疗组结合的方案。根据定量CMV－PCR结果判断其疗效。结果：更昔洛韦诱导治疗结束后转阴率为17／30（56．8％），维持治疗结束后转阴率为26／30（86．7％），CMV－DNA≤10^4/ml的患儿诱导治疗结束后的转阴率高于＞10^4/ml的患儿（P＜0．05），而且无症状性感染诱导治疗结束后的转阴率高于症状性感染（P＝0．007），维护治疗结束后两两比较均无差异。结论：更昔洛韦治疗先在性CMV感染安全有效，其疗程与CMV－DNA拷贝数大小及感染类型有关，建议对所有先天性CMV感染的患卵均应提前干预治疗。     

应用荧光定量聚合酶链反应动态观察新生儿巨细胞病毒感染

目的：探讨新生儿先天性巨细胞病毒感染后病毒转阴的规律及抗病毒治疗的效果。方法：经外周血定量CMVPCR检测确定CMV感染的37例足月新生儿，分为阿昔洛韦组和对照组，并每4周1次进行定量CMV-PCR动态观察以确定病毒转阴时间。结果：37例CMV感染中12周内阴转25例，占 67.6%，阿昔洛韦治疗组和对照组阴转时间差异无显著性。结论：先天性CMV感染多数在4周内血中病毒转阴，阿昔洛韦治疗无明显的疗效。     

更昔洛韦治疗新生儿和婴儿巨细胞病毒感染的国内外现状及建议

巨细胞病毒（cytomegalovirus,CMV）是宫内感染最常见的病毒之一,先天性CMV感染能够造成胎儿严重损害。国内外对CMV感染进行了多年研究,取得了缓慢的进展,本文对新生儿和婴儿CMV感染的更昔洛韦（ganciclovir,GCV）治疗进行讨论。     

激素治疗难治性全身型幼年特发性关节炎39例

目的观察难治性全身型幼年特发性关节炎（JIA）患儿的临床特点及糖皮质激素的治疗价值。方法全身型JIA患儿39例采用不同剂量糖皮质激素治疗,分为小剂量组：0.5～1.0mg/（kg.d）;大剂量组：1.0～1.5mg/（kg.d）。观察二组治疗10、20d后活动性指标变化,并判定疗效。结果二组使用糖皮质激素10d后总有效率分别为58.8%、72.7%,使用20d后总有效率分别为76.5%、90.9%。二组控制体温疗效无明显差异;控制压痛关节数、肿胀关节数、ESR和CRP白疗效大剂量组明显优于小剂量组（Pa〈0.05）。结论糖皮质激素对控制全身型JIA的短期疾病活动性有明显疗效,且在一定剂量范围内疗效随剂量增加而明显。     

常规剂量与小剂量促肾上腺皮质激素治疗婴儿痉挛的对照研究

目的：比较常规剂量与小剂量促肾上腺皮质激素（ACTH）治疗婴儿痉挛（West syndrome,WS）疗效及副作用的差异,寻找ACTH的最小有效剂量。方法：采用前瞻性随机对照研究,将30例WS（8例隐原性,22例症状性）随机分为常规剂量组（n=15）或小剂量组（n=15）。常规剂量组ACTH 50 IU/d×2周,随后2周减量至停药;小剂量组每日0.4 IU/kg×2周,若痉挛发作停止,随后2周减量至停药,若未完全控制或无效,加量至每日1 IU/kg 再用2周,随后用2周的时间逐渐减量至停药。比较ACTH两种不同剂量治疗WS的疗效及副作用。结果：常规剂量与小剂量治疗WS的近期疗效相似,有效率分别为53%及60%（P>0.05）,治疗后脑电图变化、痉挛复发及复发时间两组间差异无显著性（P>0.05）。8例完成12个月以上随诊,长期疗效两组间也无差异。ACTH对隐原性WS的有效率及脑电图高峰失律消失例数均高于症状性组（P<0.05）。常规剂量组副作用发生率(93%,14/15)明显高于小剂量组(20%,3/15),常规剂量组中1例出现轻度脑萎缩。结论：ACTH 50 IU/d与每日0.4 IU/kg两种剂量治疗WS的近期及远期疗效相似,对隐原性WS的疗效优于症状性,为避免副作用的发生,ACTH的使用应从小剂量（每日 0.4 IU/kg）开始。［中国当代儿科杂志,2009,11（6）：445-448］     

珂立苏治疗足月新生儿呼吸窘迫综合征临床研究

目的 研究国产外源性肺表面活性物质（珂立苏）对足月新生儿呼吸窘迫综合征（respiratory distress syndrome,RDS）的疗效。方法 本研究分为两阶段：（1）第一阶段：2011年1月至2012年6月,研究珂立苏治疗足月儿RDS的疗效。根据家长意愿将RDS患儿分为珂立苏组（74例）和固尔苏组（80例）,比较在补充外源性肺表面活性物质后两组患儿血气变化、住院时间、住院费用、重要并发症发生率及重复用药率。（2）第二阶段：2012年7月至2013年3月,比较不同剂量珂立苏治疗足月儿RDS的疗效。将接受珂立苏治疗的80例足月RDS患儿,根据胸部X线改变分为轻中度组（X线胸片Ⅱ～Ⅲ级）50例和重度组（X线胸片Ⅳ级）30例,每组又分成小剂量（每次30 ～ 40 mg/kg）和大剂量（每次70 ～ 100 mg/kg）两个亚组,比较不同剂量珂立苏对RDS的疗效。结果 第1阶段：（1）两组RDS患儿在用药前及用药后0。5h和6h,动脉血pH、PaCO2和PaO2各指标差异无统计学意义（P＞0.05）。（2）两组患儿机械通气天数、总给氧天数、住院天数及重复用药率差异无统计学意义（P＞0.05）。（3）两组患儿多脏器功能衰竭、持续性肺动脉高压、急性肾功能衰竭、气胸发生率和病死率差异无统计学意义（P＞0.05）。（4）珂立苏与固尔苏组患儿平均住院费用分别为28。778千元及31.827千元,固尔苏组患儿平均减少9.6％（P＜0.05）。第2阶段：（1）对轻中度RDS,小剂量与大剂量珂立苏治疗前及治疗后0.5h和6h,pH、PaCO2和PaO2各指标差异无统计学意义（P＞0.05）。（2）对重度RDS,大剂量珂立苏改善动脉血气的效果优于小剂量珂立苏（P＜0.05）;小剂量组与大剂量组的重复用药率分别为20.0％（3/15）和33.3％ （5/15）,大剂量组患儿平均减少40％。结论 （1）对足月儿RDS,珂立苏与固尔苏均可显著改善患儿低氧血症和高碳酸血症,两组患儿机械通气时间、总吸氧时间及住院时间相似,但珂立苏组住院费用降低。（2）对轻中度RDS,小剂量与大剂量珂立苏具有相似的临床疗效;但对重度RDS,大剂量珂立苏的疗效维持较久,并可在一定程度上减少重复用药率。     

布拉氏酵母菌联合更昔洛韦治疗巨细胞病毒感染相关性溃疡性结肠炎

目的 评价布拉氏酵母菌(亿活)联合更昔洛韦(GCV)治疗巨细胞病毒(CMV)感染相关性溃疡性结肠炎(UC)的疗效.方法 选择19例CMV染相关性UC患儿,年龄3个月～1岁,随机分为2组.治疗组12例,采用亿活(250 mg,口服,2次·d-1)联合GCV治疗;对照组7例,采用GCV治疗.对2组临床资料进行比较.结果 治疗组腹泻消失时间为(6.80±1.85)d,对照组腹泻消失时间为(9.10±1.96)d,二组比较差异有统计学意义(t=7.3,P＜0.01).治疗组血便消失时间为(4.30±1.53)d,对照组血便消失时间为(7.20±1.68)d,二组比较差异有统计学意义(t=6.2,P＜0.01).治疗4周,治疗组血CMV DNA转阴率为91.67％(11/12例),对照组转阴率为71.43％(5/7例),二组比较差异有统计学意义(x2=10.2,P＜0.01).二组治疗前后复查肝功能、肾功能均未见明显异常,治疗过程中未见不良反应.结论 联合GCV亿活治疗CMV感染相关性UC在改善腹泻、血便症状及血CMVDNA转阴率方面效果显著,未见明显不良反应.     

更昔洛韦(丽科伟)在先天性巨细胞病毒感染的临床应用

目的　 评价更昔洛韦治疗先天性巨细胞病毒 ( CMV)感染的疗效及其影响因素。 方法 　将 30例确诊为先天性CMV感染的患儿分为症状性 16例和无症状性 14例两组 ,按照更昔洛韦诱导和维持治疗相结合的方案 ,根据定量 CMV-PCR结果判断其疗效。 结果 　更昔洛韦诱导治疗结束后转阴率为 17/30 ( 5 6 .8% ) ,维持治疗结束后转阴率为 2 6 /30 ( 86 .7% ) ;CMV-DNA≤ 10 4/m l的患儿诱导治疗结束后的转阴率高于 >10 4/ml的患儿 ( P<0 .0 5 ) ,而且无症状性感染诱导治疗结束后的转阴率高于症状性感染 ( P=0 .0 0 7) ;维护治疗结束后两两比较均无差异。 结论 　更昔洛韦治疗先天性 CMV感染安全有效 ,其疗程与CMV-DNA拷贝数大小及感染类型有关 ,建议对所有先天性 CMV感染的患儿均应提前干预治疗     

Tratamiento prolongado con valganciclovir en un lactante con infección congénita por citomegalovirus

Treatment with intravenous ganciclovir for six weeks prevents hearing deterioration in children with symptomatic congenital cytomegalovirus (CMV) infection. Prolonged treatment might be more beneficial, but is associated with the potential side-effects of long-term use of intravenous lines. Oral valganciclovir could be an alternative because of its excellent bio-availability, reaching plasma concentrations similar to those achieved with intravenous ganciclovir in neonates with symptomatic CMV infection. We present a two-month-old girl with congenital CMV infection with central nervous disease involvement, who was treated with intravenous ganciclovir for 15 days followed by oral valganciclovir (30 mg/kg/day in 2 doses) for 6 months. Treatment resulted in adequate ganciclovir plasma levels, suppressed plasma viral load, prevention of hearing deterioration and was well tolerated, with no apparent side-effects.     

先天性巨细胞病毒感染抗病毒治疗的效果和安全性观察

目的：观察更昔洛韦（GCV）和（或）缬更昔洛韦（VGCV）治疗先天性巨细胞病毒（ CMV）感染患儿的疗效和不良反应。 方法：回顾性纳入2012年3月1日至2017年5月31日在复旦大学附属儿科医院（我院）新生儿科住院、确诊为先天性CMV感染的患儿,随访至2017年12月31日。从病史资料中提取患儿的一般资料,抗CMV治疗的药物和疗程,新生儿期及1、 3和6月龄的肝脾触诊检查结果、胆红素和肝功能检查指标、CMV抗体和DNA检测结果、颅脑MRI、眼底检查结果和听力检测结果,治疗期间药物的不良反应。根据抗病毒治疗与否以及疗程长短分组,比较各组的临床特征和治疗反应。 结果：28例先天性CMV感染患儿进入本文分析,其中早产儿11例,男17例;无症状/轻度症状9例,未予抗病毒治疗;中重度症状19例,GCV和（或）VGCV治疗≤6周组11例,治疗6个月组8例。①6月龄时,除1例胆汁酸轻度升高外27例中枢神经系统以外的症状和体征、胆红素、肝功能和血常规均恢复正常。②无症状／轻度症状组1例在6月龄时出现左侧听力中度损失。治疗≤6周组中,2例CMV相关眼底病变于1月龄时消失; 颅脑MRI异常信号和听力损失者各5例,6月龄时分别有3例和2例无改善。治疗6个月组中,4例先天性CMV感染相关视网膜病变在随访中均消失;3例头颅MRI异常信号者和7例有听力损失者,6月龄时分别有2例和1例无改善。③治疗≤6周组和治疗6个月组在6月龄时中枢神经系统病变改善情况差异无统计学意义。④治疗过程中未发现与GCV和VGCV应用相关的粒细胞减少和肝功能异常。 结论：抗病毒治疗能改善感音神经性耳聋和脉络膜视网膜炎,GCV和（或）VGCV≤6周与6个月的治疗效果相近;建议对无临床症状先天性CMV感染患儿行眼底检查、脑干诱发电位和头颅MRI检查。     

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation

Lapidus‐Krol E, Shapiro R, Amir J, Davidovits M, Steinberg R, Mor E, Avitzur Y. The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.
Pediatr Transplantation 2010: 14:753–760. © 2010 John Wiley & Sons A/S. Abstract: Routine prophylaxis for CMV with valganciclovir is common in adult recipients but data to support its use in children are scarce. The aim of this study was to compare the efficacy and safety of valganciclovir vs. ganciclovir in a pediatric cohort. We performed a retrospective analysis of 92 children after KTx and/or LTx. All children have received IV ganciclovir for two wk, and then oral ganciclovir (TID; n = 41) before 2004, or valganciclovir (OD; n = 51) thereafter. Treatment was given for three months in R+/D+ or R+/D− recipients and for six months in R−/D+. Patients were followed for one yr post transplant. Both groups were comparable in their demographic and transplant‐related history. Symptomatic CMV infection/disease developed in 13.7% vs. 19.5% of valganciclovir and ganciclovir groups, respectively (P‐NS). Time‐to‐onset of CMV infection was comparable in both groups (P‐NS); rates of acute allograft rejection were similar in both groups (3.9% vs. 9.8%). Risk factors for CMV infection included young age, serostatus of R−/D+, and allograft from cadaver donor. No significant side effects were noted in both groups. As in adults, valganciclovir appears to be as efficacious and safe as oral ganciclovir. Valganciclovir should be considered as a possible prophylactic treatment for CMV in pediatric recipients of KTx or LTx.     

Disposition of an immunoglobulin intravenous preparation in very low birth weight neonates

To assess the disposition, tolerance, and toxicity of an intravenous preparation of immunoglobulin (IGIV) in very low birth weight (VLBW) neonates, we administered single doses of 500 or 750 mg/kg to 20 neonates with birth weights between 750 and 1500 g during the first week of life. The infusion of this product was well tolerated. Modest changes in hemoglobin, hematocrit, and total hemolytic complement occurred as expected. Hepatic toxic effects were not detected. Mean peak IgG concentrations were 1564 and 1316 mg/dL for the high-dose and low-dose groups, respectively. Mean IgG concentrations were very similar for both groups on postinfusion days 1, 4, 7, 14, 21, and 28. IgG concentrations remained above 300 mg/dL in seven of 10 infants in each group by day 21, and in six of the high-dose group and seven of the low-dose group by day 28. Mean elimination half-lives were 22.6 and 22.8 days in the high-dose and low-dose groups, respectively. These data provide a basis for assessment of potential efficacy of IGIV in the prevention of late-onset infection in VLBW neonates.     

新生儿室管膜下囊肿的病因研究

为了探讨新生儿室管膜下囊肿（ＳＥＣ）与先天性感染的关系，采用ＥＬＩＳＡ酶标法检测母婴双方囊肿组与对照组各７０例血巨细胞病毒（ＣＭＶ）、风疹病毒、弓形虫的抗体，并应用聚合酶链反应（ＰＣＲ）技术直接检测病原ＤＮＡ（风疹病毒除外），同时作尿ＣＭＶ的ＰＣＲ检测。结果：囊肿组新生儿血ＣＭＶ－ＩｇＭ抗体和ＣＭＶ－ＰＣＲ阳性率显著高于对照组（分别为１７．１％、５．７％和１２．９％、２．９％）；且尿ＣＭＶ－ＰＣＲ的阳性率达４０．０％（２８／７０），高于对照组的１７．１％（１２／７０）；分别进行两组自身对照，尿ＣＭＶ－ＰＣＲ的阳性率显著高于血ＣＭＶ－ＰＣＲ阳性率（Ｐ＜０．０５）。囊肿组母亲的尿ＣＭＶ－ＰＣＲ阳性率亦显著高于对照组（３０％、１０％、Ｐ＜０．０１）。提示新生儿ＳＥＣ是宫内感染损害中枢神经系统的表现之一，与先天性ＣＭＶ感染有关，尿ＣＭＶ－ＰＣＲ检查可作为宫内ＣＭＶ感染的首选实验室诊断方法。     

Cytomegalovirus hepatitis and ganciclovir treatment in immunocompetent children

Ganciclovir treatment in children with cytomegalovirus (CMV) infection is still controversial and only indicated in selected cases. The aim of thi study was to evaluate clinical and demographic features of CMV hepatitis in immunocompetent children and to determine the effect of ganciclovir treatment in these patients retrospectively. The study was carried out in a group o 29 children with CMV hepatitis. All the patients were investigated for signs of infection, inborn errors of metabolism, genetic diseases, extrahepatic biliary atresia and other causes of hepatitis. Two patients with congenital CMV infection and two patients with biliary atresia were excluded from the study group. The patients included in the study were divided into two groups: non-cholestatic hepatitis (n=16) as Group I and cholestatic hepatitis (n=9) as Group II. Four (25%) patients in the non-cholestatic group and four (44.4 in the cholestatic group were treated with ganciclovir for a median of 21 days. The mean age was 9.6+/- 10.9 months (median age 6 months) in Group I, while cholestatic hepatitis patients in Group II were significantly younger, with a mean age of 2.7+/-0.9 months (p<0.01). The most prominent symptoms at admission were diarrhea and vomiting (25%) in Group I. In Group I, all cases (100%) and in Group II, three of four cases (75%) treated with ganciclovir had recovery from acute CMV hepatitis. In the non-cholestatic group, no relapses were observed while one patient in the cholestatic group relapsed and progressed into chronic liver disease. Patients who received supportive treatment showed a marked decrease in GGT, ALT, AST and bilirubin levels spontaneously and no relapses of hepatitis were observed in at least one year of follow-up. Although ganciclovir therapy is not indicated particularly in immunocompetent cases, since most were self-limited infections, in case of progressive and persistent hepatitis, such as in our cases, ganciclovir was a treatment option; no side effect due to ganciclovir therapy was observed in our cases. Although ganciclovir seems to be effective in progressive CMV hepatitis, multicenter randomized studies in a large study group are necessar to determine the efficacy and indications for ganciclovir treatment.     

Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir

Congenital cytomegalovirus infection is the most common cause of nonhereditary sensorineural hearing loss and an important cause of psychomotor retardation. Earlier studies showed that 6-weeks’ treatment with ganciclovir, starting in the neonatal period, prevented hearing deterioration at 6 months, but in one-fifth of the infants, the effect was not sustained at age 12 months. The aim of this preliminary retrospective study was to investigate the effectiveness and safety of long-term treatment with ganciclovir/valganciclovir for congenital cytomegalovirus infection. Twenty-three infants with culture-proven symptomatic congenital cytomegalovirus infection were treated with ganciclovir for 6 weeks followed by oral valganciclovir to age 12 months. Audiometry was performed at least three times in the first year, in addition to physical examination including neurological and developmental assessment. At age ≥1 year, hearing was normal in 76% of affected ears compared to baseline (54%). In 25 normal ears at birth no deterioration was found at ≥1 year. These results were significantly better than reported in a historical control group of similar infants treated for 6 weeks only (P= 0.001). Viral load monitoring demonstrated sustained virological response. Four of the children (18%) had mental retardation. The main side effect of treatment was transient neutropenia. In conclusion, prolonged therapy of symptomatic congenital CMV infection with intravenous ganciclovir followed by oral valganciclovir is safe, and it appears to lead to a better auditory outcome than short-term treatment.     

Cytomegalovirus infection after allogeneic stem cell transplant in children

The aim of this study was to examine the frequency and the course of cytomegalovirus (CMV) infection and CMV disease in a group of pediatric and adolescent patients after allogeneic stem cell transplantation. Patients were treated according to a protocol including prophylactic high-dose acyclovir in combination with preemptive administration of ganciclovir, based on weekly examinations of CMV antigenemia. A total of 110 consecutively transplanted patients, with a mean age of 9 yr (range 0-20) were treated according to the protocol. All patients were transplanted between March 1993 and January 2000 at the only Danish allotransplantation center. CMV infection occurred in 21.8% (24 of 110) of the patients. Three patients [12.5% (3/24)] developed CMV disease, all with pneumonitis and one with gastrointestinal disease as well. Mean time of disease onset was day +58. Treatment with ganciclovir was in general well tolerated. Late onset CMV disease was not documented. Multivariate analysis revealed that the use of unrelated donor transplants was significantly associated with an increased risk for CMV infection [hazard ratio (HR) 2.90, p = 0.03] and CMV infection was found to be a risk factor for transplant related mortality before day +100 (HR 10.70, p = 0.0015). Although high-dose acyclovir in combination with antigenemia based preemptive treatment with ganciclovir resulted in a low incidence of CMV disease in pediatric and adolescent patients, CMV infection was a significant risk factor in stem cell transplantation with unrelated donors.     

不同维持剂量枸橼酸咖啡因治疗极低出生体重早产儿呼吸暂停的前瞻性随机对照研究

目的分析不同维持剂量枸橼酸咖啡因治疗极低出生体重早产儿呼吸暂停的疗效及安全性。方法将2016年1月至2018年1月收治的诊断为原发性呼吸暂停的极低出生体重早产儿78例随机分为高剂量咖啡因组（n=38）及低剂量咖啡因组（n=40）。两组均采取相同的枸橼酸咖啡因负荷量20 mg/kg治疗，24 h后分别给予每日10 mg/kg及5 mg/kg的维持剂量，观察比较两组患儿治疗的有效率及不良反应的发生率。结果高剂量咖啡因组治疗有效率（71%）高于低剂量咖啡因组（48%）（P < 0.05）；呼吸暂停持续时间、咖啡因治疗时间均较低剂量咖啡因组明显缩短（P < 0.05）。两组住院时间、心动过速及喂养不耐受发生率，以及支气管肺发育不良、坏死性小肠结肠炎及颅内出血的发生率比较差异无统计学意义（P > 0.05）。两组间病死率比较差异无统计学意义（P > 0.05）。结论高维持剂量枸橼酸咖啡因治疗极低出生体重早产儿呼吸暂停的效果优于低维持剂量咖啡因，而且未增加相关药物不良反应和早产儿严重并发症的发生率。