Supplementary Material for: Systematic Review and Meta-Analysis of Cardiovascular Medications in Neonatal Hypotension

Background: Comparative studies among the various cardiovascular medications used for the treatment of neonatal hypotension are lacking. Methods: This systematic review and pairwise meta-analysis of the anti-hypotensive treatments in preterm and term infants was conducted to evaluate efficacy and impact on outcome. Electronic databases were searched up to February 2021 for relevant articles. As an extension of the current approach for study selection, a machine learning technique was used. Only randomized controlled trials (RCTs) of inotropes, pressors, volume therapy, and corticosteroids were included. Response to treatment was the primary outcome while secondary outcomes included mortality and common morbidities. Results: Nineteen RCTs involving 758 preterm and term neonates were found, and 8 treatments were evaluated. Most studies involved subjects with early hypotension associated with prematurity. Pairwise meta-analysis among treatments showed that dopamine was more effective than dobutamine regarding the response to treatment (restoration of normotension or normalization of blood pressure) (7 trials, 286 neonates, odds ratio, 3.06 [95% CI = 1.06–8.87]; I2 = 49%, very low quality of the evidence per GRADE). Comparisons of other treatments were not significant. No differences were found among regimens regarding survival and other secondary outcomes. Conclusion: In this systematic review and pairwise meta-analysis, only the comparison of dopamine versus dobutamine provided evidence for efficacy of treatment and favored dopamine. No safe conclusions could be reached in regard to other treatments. Data regarding the management of arterial hypotension in conditions other than transition after birth in preterm newborns are sparse both in preterm and term infants.

研究背景：目前针对用于治疗新生儿低血压的各类心血管药物开展的对比研究尚较为匮乏。
研究方法：本研究针对早产与足月新生儿的抗低血压治疗方案开展系统综述及两两Meta分析，旨在评估其疗效及对临床结局的影响。我们检索了截至2021年2月的电子数据库以获取相关研究文献；作为现有文献筛选流程的拓展，本研究引入了机器学习技术辅助筛选。本研究仅纳入针对正性肌力药、升压药、液体治疗及糖皮质激素的随机对照试验（Randomized Controlled Trials, RCTs），将治疗应答率设为主要结局指标，次要结局指标则包括病死率及常见并发症发生率。
研究结果：最终共纳入19项随机对照试验，涉及758名早产及足月新生儿，共评估了8种治疗方案。多数研究的研究对象为合并早产儿早期低血压的人群。各治疗方案的两两Meta分析结果显示，在治疗应答（恢复正常血压或血压达标）方面，多巴胺的疗效优于多巴酚丁胺（共7项试验，286名新生儿，比值比为3.06，95%置信区间：1.06~8.87；I²=49%，依据推荐分级的评估、制订与评价系统（Grading of Recommendations Assessment, Development and Evaluation, GRADE），证据质量极低）。其余治疗方案间的比较未发现显著差异；各治疗方案在生存率及其他次要结局指标方面均未观察到显著差异。
研究结论：本系统综述及两两Meta分析结果显示，仅多巴胺与多巴酚丁胺的对比研究提供了明确的治疗疗效证据，且证实多巴胺更具优势。其余治疗方案的疗效均未得出可靠结论。针对早产新生儿出生过渡期以外的其他场景下动脉低血压的管理相关数据，在早产及足月新生儿群体中均较为匮乏。