BACKGROUND While porcine seems to be superior to bovine surfactants in terms of respiratory outcomes, it is unclear if a surfactant can improve extra-pulmonary outcomes in preterm neonates with respiratory distress syndrome and if there is any physiopathological/biological mechanism linking surfactant therapy to these outcomes. We aim to fill these knowledge gaps. METHODS Systematic and pragmatic review coupled with meta-analysis of randomized controlled trials of bovine or porcine surfactants administered to treat RDS in preterm neonates; common extra-pulmonary neonatal intensive care outcomes were considered. As additional analysis, animal or human translational studies about mechanisms linking surfactant replacement to extra-pulmonary neonatal outcomes were also systematically reviewed. RESULTS Porcine surfactant is associated with lower incidence of patent ductus arteriosus (OR:0.655; 95%CI:0.460-0.931); p = 0.018; 12 trials; 1472 patients); prenatal steroids (coeff.:-0.009, 95%CI:-0.03-0.009, p = 0.323) and gestational age (coeff.:0.079, 95%CI:-0.18-0.34, p = 0.554) did not influence this effect size. No significant differences were found between porcine and bovine surfactants on neonatal intensive care unit length of stay (mean difference (days):-2.977; 95%CI:-6.659-0.705; p = 0.113; 8 trials; 855 patients), intra-ventricular hemorrhage of any grade (OR:0.860; 95%CI:0.648-1.139); p = 0.293; 15 trials; 1703 patients), severe intra-ventricular hemorrhage (OR:0.852; 95%CI:0.624-1.163); p = 0.313; 15 trials; 1672 patients), necrotizing entero-colitis (OR:1.190; 95%CI:0.785-1.803); p = 0.412; 9 trials; 1097 patients) and retinopathy of prematurity (OR:0.801; 95%CI:0.480-1.337); p = 0.396; 10 trials; 962 patients). CONCLUSIONS Physiopathological mechanisms explaining the effect of surfactant have been found for patent ductus arteriosus only, while they are lacking for all other endpoints. Porcine surfactant is associated with lower incidence of PDA than bovine surfactants. As there are no differences in terms of other extra-pulmonary outcomes and no physiopathological plausibility, these endpoints should not be used in future trials. REGISTRATION PROSPERO n.CRD42018100906.

中文翻译：

---

猪与牛表面活性剂治疗早产儿 RDS：实用荟萃分析和回顾对肺外结果影响的生理病理学合理性。

背景 虽然猪在呼吸结果方面似乎优于牛表面活性剂，但尚不清楚表面活性剂是否可以改善患有呼吸窘迫综合征的早产新生儿的肺外结果，以及是否存在将表面活性剂治疗与这些结果联系起来的任何生理病理学/生物学机制. 我们的目标是填补这些知识空白。方法 对牛或猪表面活性剂用于治疗早产儿 RDS 的随机对照试验进行系统和务实的回顾以及荟萃分析；考虑了常见的肺外新生儿重症监护结果。作为额外的分析，关于将表面活性剂替代与肺外新生儿结局联系起来的机制的动物或人类转化研究也进行了系统评价。结果猪表面活性剂与较低的动脉导管未闭发生率相关（OR：0.655；95%CI：0.460-0.931）；p = 0.018；12 次试验；1472 名患者）；产前类固醇 (coeff.:-0.009, 95%CI:-0.03-0.009, p = 0.323) 和胎龄 (coeff.:0.079, 95%CI:-0.18-0.34, p = 0.554) 不影响此效应大小. 猪和牛表面活性剂对新生儿重症监护病房的住院时间没有显着差异（平均差异（天）：-2.977；95%CI：-6.659-0.705；p = 0.113；8 项试验；855 名患者），任何级别的脑室出血（OR：0.860；95%CI：0.648-1.139）；p = 0.293；15 次试验；1703 名患者），严重脑室内出血（OR：0.852；95%CI：0.624-1.163）；p = 0.313；15 次试验；1672 名患者），坏死性小肠结肠炎（OR：1.190；95%CI：0.785-1.803）；p = 0.412；9 次试验；1097 名患者）和早产儿视网膜病变（OR：0.801；95%CI：0.480-1.337）；p = 0.396；10 次试验；962 名患者）。结论 仅在动脉导管未闭中发现了解释表面活性剂作用的生理病理学机制，而对于所有其他终点均缺乏这些机制。与牛表面活性剂相比，猪表面活性剂与 PDA 的发生率较低有关。由于在其他肺外结果方面没有差异，也没有病理生理学的合理性，这些终点不应在未来的试验中使用。注册 PROSPERO n.CRD42018100906。与牛表面活性剂相比，猪表面活性剂与 PDA 的发生率较低有关。由于在其他肺外结果方面没有差异，也没有病理生理学的合理性，这些终点不应在未来的试验中使用。注册 PROSPERO n.CRD42018100906。与牛表面活性剂相比，猪表面活性剂与 PDA 的发生率较低有关。由于在其他肺外结果方面没有差异，也没有病理生理学的合理性，这些终点不应在未来的试验中使用。注册 PROSPERO n.CRD42018100906。