Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada2Division of Neonatology, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia.
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
JAMA Pediatr. 2017 Jun 1;171(6):564-572. doi: 10.1001/jamapediatrics.2017.0238.
Caffeine citrate therapy for apnea of prematurity reduces the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability at 18 months and may improve motor function at 5 years.
To evaluate whether neonatal caffeine therapy is associated with improved functional outcomes 11 years later.
DESIGN, SETTING, AND PARTICIPANTS: A follow-up study was conducted at 14 academic hospitals in Canada, Australia, and the United Kingdom from May 7, 2011, to May 27, 2016, of English- or French-speaking children who had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between October 11, 1999, and October 22, 2004. A total of 1202 children with birth weights of 500 to 1250 g were eligible for this study; 920 (76.5%) had adequate data for the main outcome.
Caffeine citrate or placebo until drug therapy for apnea of prematurity was no longer needed.
Functional impairment was a composite of poor academic performance (defined as at least 1 standard score greater than 2 SD below the mean on the Wide Range Achievement Test-4), motor impairment (defined as a percentile rank of ≤5 on the Movement Assessment Battery for Children-Second Edition), and behavior problems (defined as a Total Problem T score ≥2 SD above the mean on the Child Behavior Checklist).
Among the 920 children (444 females and 476 males; median age, 11.4 years [interquartile range, 11.1-11.8 years]), the combined rates of functional impairment were not significantly different between the 457 children assigned to receive caffeine compared with the 463 children assigned to receive placebo (145 [31.7%] vs 174 [37.6%]; adjusted odds ratio, 0.78; 95% CI, 0.59-1.02; P = .07). With all available data, including those from up to 24 Swedish trial participants, the rates of poor academic performance on 1 or more of 4 subtests (66 of 458 [14.4%] vs 61 of 462 [13.2%]; adjusted odds ratio, 1.11; 95% CI, 0.77-1.61; P = .58) and behavior problems (52 of 476 [10.9%] vs 40 of 481 [8.3%]; adjusted odds ratio, 1.32; 95% CI, 0.85-2.07; P = .22) were broadly similar between the group that received caffeine and the group that received placebo. However, caffeine therapy was associated with a reduced risk of motor impairment compared with placebo (90 of 457 [19.7%] vs 130 of 473 [27.5%]; adjusted odds ratio, 0.66; 95% CI, 0.48-0.90; P = .009).
Caffeine therapy for apnea of prematurity did not significantly reduce the combined rate of academic, motor, and behavioral impairments but was associated with a reduced risk of motor impairment in 11-year-old children with very low birth weight. At the doses used in this trial, neonatal caffeine therapy is effective and safe into middle school age.
clinicaltrials.gov Identifier: NCT00182312; isrctn.org Identifier: ISRCTN44364365.
咖啡因柠檬酸盐疗法可降低早产儿呼吸暂停的支气管肺发育不良、严重视网膜病变和 18 个月时神经发育障碍的发生率，并可能改善 5 岁时的运动功能。
评估新生儿咖啡因治疗是否与 11 年后的功能结果改善相关。
设计、地点和参与者：一项随访研究于 2011 年 5 月 7 日至 2016 年 5 月 27 日在加拿大、澳大利亚和英国的 14 家学术医院进行，纳入了 1999 年 10 月 11 日至 2004 年 10 月 22 日之间参加咖啡因治疗早产儿呼吸暂停随机、安慰剂对照试验的英语或法语儿童；共有 1202 名出生体重为 500 至 1250 g 的儿童符合本研究条件；920 名（76.5%）有主要结局的足够数据。
咖啡因柠檬酸盐或安慰剂，直到早产儿呼吸暂停的药物治疗不再需要。
功能障碍是学业成绩不佳（定义为在宽范围成就测试-4 中至少比平均标准得分高 2 个标准差）、运动障碍（定义为运动评估电池的百分位数排名≤儿童第二版）和行为问题（定义为儿童行为检查表的总问题 T 得分高于平均值 2 个标准差）的综合表现。
在 920 名儿童（444 名女性和 476 名男性；中位数年龄为 11.4 岁[四分位间距，11.1-11.8 岁]）中，接受咖啡因治疗的 457 名儿童与接受安慰剂治疗的 463 名儿童的功能障碍综合发生率无显著差异（145[31.7%]比 174[37.6%]；调整后的优势比，0.78；95%置信区间，0.59-1.02；P=0.07）。在所有可用数据中，包括多达 24 名瑞典试验参与者的数据中，4 项测试中有 1 项或多项成绩不佳的发生率（458 名中的 66 名[14.4%]比 462 名中的 61 名[13.2%]；调整后的优势比，1.11；95%置信区间，0.77-1.61；P=0.58）和行为问题（476 名中的 52 名[10.9%]比 481 名中的 40 名[8.3%]；调整后的优势比，1.32；95%置信区间，0.85-2.07；P=0.22）在接受咖啡因治疗的组和接受安慰剂治疗的组之间大致相似。然而，与安慰剂相比，咖啡因治疗与运动障碍风险降低相关（457 名中的 90 名[19.7%]比 473 名中的 130 名[27.5%]；调整后的优势比，0.66；95%置信区间，0.48-0.90；P=0.009）。
早产儿呼吸暂停的咖啡因治疗并未显著降低学业、运动和行为障碍的综合发生率，但与极低出生体重的 11 岁儿童的运动障碍风险降低相关。在本试验中使用的剂量下，新生儿咖啡因治疗在进入中学时代时是有效和安全的。
临床试验.gov 标识符：NCT00182312；ISRCTN 标识符：ISRCTN44364365。
