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). CONCLUSION 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.

中文翻译：

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早产儿的早期与晚期咖啡因治疗管理：更新的系统评价和荟萃分析。

背景技术咖啡因通常用于治疗早产儿呼吸暂停，并且已显示出预防早产新生儿其他病症的潜力。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摄入咖啡因的结果。方法 在 PubMed、Embase 和 Cochrane 图书馆中检索比较早产儿 0-2 天至 ≥3 天咖啡因摄入的研究。结局包括死亡率、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、住院时间和综合情况BPD 或死亡。使用RevMan 5.4.1进行统计分析。结果 11项研究共纳入122,579名患者，其中2项为随机对照试验（RCT），63.9%的新生儿接受了早期咖啡因给药。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）、迟发性脓毒症（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着降低。早期咖啡因组的 BPD 或死亡综合结果也较低（OR：0.76；95% CI：[0.66-0.88]；p < 0.0003）。早期咖啡因组的死亡率较高（OR：1.20；95% CI：1.12-1.29；p < 0.001）。结论 与晚服咖啡因相比，早服咖啡因与早产儿 BPD、IVH、ROP、迟发性败血症和 PDA 的减少有关，尽管死亡率有所增加。需要进行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可能与有利于晚期治疗组的观察性研究中的生存偏差有关。