Abstract：
BACKGROUND: Caffeine is commonly used as therapy for apnea of prematurity and has shown potential in preventing other conditions in preterm neonates. However, the optimal timing for caffeine therapy remains uncertain.
OBJECTIVE: This study aimed to compare the outcomes of early versus late administration of caffeine in preterm neonates.
METHODS: PubMed, Embase, and Cochrane Library were searched for studies comparing 0-2 days to ≥3 days caffeine introduction in preterm neonates. Outcomes included were mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), late-onset sepsis, length of hospital stay, and the composite of BPD or death. RevMan 5.4.1 was used for statistical analysis.
RESULTS: A total of 122,579 patients from 11 studies were included, 2 were randomized controlled trials (RCTs), and 63.9% of the neonates received early caffeine administration. The rates of BPD (OR: 0.70; 95% CI: [0.60-0.81]; p < 0.0001), IVH (OR: 0.86; 95% CI: [0.82-0.90]; p < 0.0001), ROP (OR: 0.80; 95% CI: [0.74-0.86]; p < 0.0001), late-onset sepsis (OR: 0.84; 95% CI: [0.79-0.89]; p < 0.00001), and PDA (OR: 0.60; 95% CI: [0.47-0.78]; p < 0.0001) were significantly reduced in the early caffeine group. The composite outcome of BPD or death was also lower in the early caffeine group (OR: 0.76; 95% CI: [0.66-0.88]; p < 0.0003). Mortality rate was higher in the early caffeine group (OR: 1.20; 95% CI: 1.12-1.29; p < 0.001).
CONCLUSIONS: As compared with late caffeine administration, early caffeine is associated with a reduction in BPD, IVH, ROP, late-onset sepsis, and PDA in preterm neonates, albeit increased mortality. Additional RCTs are warranted to confirm these findings and evaluate whether the effect on mortality may be related to survival bias in observational studies favoring the late treatment group.
OBJECTIVE: This study aimed to compare the outcomes of early versus late administration of caffeine in preterm neonates.
METHODS: PubMed, Embase, and Cochrane Library were searched for studies comparing 0-2 days to ≥3 days caffeine introduction in preterm neonates. Outcomes included were mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), late-onset sepsis, length of hospital stay, and the composite of BPD or death. RevMan 5.4.1 was used for statistical analysis.
RESULTS: A total of 122,579 patients from 11 studies were included, 2 were randomized controlled trials (RCTs), and 63.9% of the neonates received early caffeine administration. The rates of BPD (OR: 0.70; 95% CI: [0.60-0.81]; p < 0.0001), IVH (OR: 0.86; 95% CI: [0.82-0.90]; p < 0.0001), ROP (OR: 0.80; 95% CI: [0.74-0.86]; p < 0.0001), late-onset sepsis (OR: 0.84; 95% CI: [0.79-0.89]; p < 0.00001), and PDA (OR: 0.60; 95% CI: [0.47-0.78]; p < 0.0001) were significantly reduced in the early caffeine group. The composite outcome of BPD or death was also lower in the early caffeine group (OR: 0.76; 95% CI: [0.66-0.88]; p < 0.0003). Mortality rate was higher in the early caffeine group (OR: 1.20; 95% CI: 1.12-1.29; p < 0.001).
CONCLUSIONS: As compared with late caffeine administration, early caffeine is associated with a reduction in BPD, IVH, ROP, late-onset sepsis, and PDA in preterm neonates, albeit increased mortality. Additional RCTs are warranted to confirm these findings and evaluate whether the effect on mortality may be related to survival bias in observational studies favoring the late treatment group.
摘要：
背景：咖啡因通常用作早产儿呼吸暂停的治疗，并已显示出预防早产新生儿其他疾病的潜力。然而,咖啡因治疗的最佳时机仍不确定.
目的：本研究旨在比较早产儿早期和晚期咖啡因给药的结局。
方法：PubMed，Embase,和Cochrane图书馆进行了比较研究，比较了早产新生儿中0-2天和≥3天咖啡因的引入。结果包括死亡率，支气管肺发育不良（BPD），脑室内出血（IVH），坏死性小肠结肠炎（NEC），早产儿视网膜病变（ROP），动脉导管未闭(PDA),迟发性败血症,住院时间,以及BPD或死亡的复合物。采用RevMan5.4.1进行统计分析。
结果：共纳入来自11项研究的122,579名患者，2是随机对照试验（RCTs），63.9%的新生儿接受了早期咖啡因治疗。BPD率（OR：0.70；95%CI：[0.60-0.81]；p＆lt;0.0001），IVH（OR：0.86；95%CI：[0.82-0.90]；p＆lt;0.0001），ROP（OR：0.80；95%CI：[0.74-0.86]；p＆lt;0.0001），晚发性脓毒症（OR：0.84;95%CI：[0.79-0.89];p<0.00001），和PDA(OR:0.60;95%CI:[0.47-0.78];p<0.0001)在早期咖啡因组中显著降低。早期咖啡因组BPD或死亡的复合结局也较低(OR:0.76;95%CI:[0.66-0.88];p<0.0003)。早期咖啡因组死亡率较高(OR:1.20;95%CI:1.12-1.29;p<0.001)。
结论：与晚期咖啡因给药相比，早期咖啡因与BPD的减少有关，IVH,拖放,迟发性败血症,早产儿的PDA，尽管死亡率增加。在支持晚期治疗组的观察性研究中，需要额外的随机对照试验来证实这些发现，并评估对死亡率的影响是否与生存偏倚有关。
目的：本研究旨在比较早产儿早期和晚期咖啡因给药的结局。
方法：PubMed，Embase,和Cochrane图书馆进行了比较研究，比较了早产新生儿中0-2天和≥3天咖啡因的引入。结果包括死亡率，支气管肺发育不良（BPD），脑室内出血（IVH），坏死性小肠结肠炎（NEC），早产儿视网膜病变（ROP），动脉导管未闭(PDA),迟发性败血症,住院时间,以及BPD或死亡的复合物。采用RevMan5.4.1进行统计分析。
结果：共纳入来自11项研究的122,579名患者，2是随机对照试验（RCTs），63.9%的新生儿接受了早期咖啡因治疗。BPD率（OR：0.70；95%CI：[0.60-0.81]；p＆lt;0.0001），IVH（OR：0.86；95%CI：[0.82-0.90]；p＆lt;0.0001），ROP（OR：0.80；95%CI：[0.74-0.86]；p＆lt;0.0001），晚发性脓毒症（OR：0.84;95%CI：[0.79-0.89];p<0.00001），和PDA(OR:0.60;95%CI:[0.47-0.78];p<0.0001)在早期咖啡因组中显著降低。早期咖啡因组BPD或死亡的复合结局也较低(OR:0.76;95%CI:[0.66-0.88];p<0.0003)。早期咖啡因组死亡率较高(OR:1.20;95%CI:1.12-1.29;p<0.001)。
结论：与晚期咖啡因给药相比，早期咖啡因与BPD的减少有关，IVH,拖放,迟发性败血症,早产儿的PDA，尽管死亡率增加。在支持晚期治疗组的观察性研究中，需要额外的随机对照试验来证实这些发现，并评估对死亡率的影响是否与生存偏倚有关。
