Gray Peter H, Flenady Vicki J, Charles Bruce G, Steer Peter A
Department of Neonatology and Mater Mothers' Research Centre, Mater Mothers' Hospital, The University of Queensland, Australia.
J Paediatr Child Health. 2011 Apr;47(4):167-72. doi: 10.1111/j.1440-1754.2010.01943.x. Epub 2011 Jan 18.
To compare two dosing regimens for caffeine citrate for neonates born less than 30 weeks gestation in terms of development, temperament and behaviour.
A multi-centre, randomised, controlled trial design was undertaken. A total of 287 infants with apnoea of prematurity or in the peri-extubation period were randomised to receive one of two dosage regimens (20 vs. 5 mg/kg/day). The main outcome measure was cognitive development at 1 year of age on the Griffiths Mental Development Scales. Secondary outcome measures included neonatal morbidity, death and disability, temperament at 1 year and behaviour at 2 years of age.
Data on the primary outcome were available for 190 survivors at 12 months corrected for prematurity. A significantly greater mean general quotient was found in the high-dose group (mean (standard deviation), 98.0 (13.8) vs. 93.6 (16.5), P = 0.048). On omission of two infants for whom cognitive assessment was not possible because of disability while the mean general quotient remained higher for infants in the high-dose group, this was no longer statistically significant (P= 0.075). There was a non-significant trend for benefit in the high-dose caffeine group for death or major disability, 15.4% versus 24.2%; relative risk 0.75 (95% confidence interval 0.49-1.14). No differences in the mean values between the two groups were shown for temperament and behaviour.
Caffeine citrate with a dosage regimen of 20 mg/kg/day did not result in adverse outcomes for development, temperament and behaviour. The borderline benefit in cognition with high-dose caffeine needs further investigation.
比较两种枸橼酸咖啡因给药方案对孕周小于30周的新生儿在发育、气质和行为方面的影响。
采用多中心、随机、对照试验设计。共有287例早产呼吸暂停或处于拔管期的婴儿被随机分为接受两种给药方案之一（20mg/kg/天与5mg/kg/天）。主要结局指标是1岁时使用格里菲斯心理发展量表评估的认知发展。次要结局指标包括新生儿发病率、死亡和残疾情况，1岁时的气质以及2岁时的行为。
校正早产因素后，12个月时190例存活者有主要结局的数据。高剂量组的平均总商数显著更高（平均值（标准差），98.0（13.8）对93.6（16.5），P = 0.048）。由于残疾而无法进行认知评估的两名婴儿被排除后，高剂量组婴儿的平均总商数仍然更高，但此时差异不再具有统计学意义（P = 0.075）。高剂量咖啡因组在死亡或严重残疾方面有不显著的获益趋势，分别为15.4%对24.2%；相对风险0.75（95%置信区间0.49 - 1.14）。两组在气质和行为方面的平均值没有差异。
20mg/kg/天给药方案的枸橼酸咖啡因对发育、气质和行为未产生不良后果。高剂量咖啡因在认知方面的临界获益需要进一步研究。
