Our study showed that the survival rate of neonates with respiratory failure after receiving VV ECMO treatment was as high as 88% at hospital discharge, even higher than that (73%) of neonates with respiratory failure treated by ECMO according to ELSO registry report in January 2019 . The reason might be that the data of ELSO come from the mixed population of VA ECMO and VV ECMO, and the patients who received VA ECMO mostly had hemodynamic instability and needed cardiac support, thus reduce the survival rate. According to the ELSO database, the survival rate of VA ECMO in the treatment of neonatal respiratory failure between 2012 and 2017 was 70%, while that of VV ECMO was 80% .
Our results also showed that among the included studies, the mortality rate of patients in the kugdman et al’s  study was lowest, while that in the Chevalier et al’s  study was highest. On one hand, neonates with MAS enrolled in the kugdman et al’s study might have more stable respiratory status, plus some new treatment modalities (NO, HFV, surfactant) were used and the ECMO team was more experienced during this time, thus improve the survival rate. On another hand, in the Chevalier et al’s study, cannula applied on neonates was small, which means this group of neonates were small, and at that time ECMO equipment was not advanced, team of VV ECMO was not so experienced, these factors might result in the relatively high mortality of this study.
Since a double-lumen catheter was designed in 1989, VV ECMO was increasingly used in neonatal respiratory failure, and ligation of the carotid artery was avoided [23-24]. Over the years, many studies have reported the benefits of VV ECMO for neonatal respiratory failure. Roberts et al  in a single center study compared double-lumen venovenous extracorporeal membrane oxygenation with cephalic draining cannula (VVDL+V ECMO) with data as collected in the ELSO database, with survival rate of 89.1% and 68.7%, respectively. They concluded that VVDL+V approach was associated with improved survival and lower rates of complication as compared with the ELSO database. Fukuda et al  also compared VA with VV access in the cerebral circulation of newborn infants during extracorporeal membrane oxygenation, the results showed that neonates with severe pulmonary failure can be effectively supported by VV ECMO. In addition to stable hemodynamics of the brain compared with VA ECMO, it has advantages in myocardial and pulmonary vascular oxygenation, resulting in favorable cerebral hemodynamics. Moreover, many studies have showed that VV ECMO compared favorably to VA ECMO for cardiovascular support [27-28]. Several other previous studies have also showed that VV ECMO was associated to lower rates of neurologic complications as compared with VA ECMO [23,29-30]. Some potential advantages of VV ECMO over VA ECMO might explain the results. During VV ECMO, ligation of arteries was avoided, pulmonary circulation and coronary artery perfusion were maintained well, thus left ventricular afterload was reduced. However, a significant number of system-related complications, including pneumothorax, hypertension, seizure, renal failure, hemorrhage and so on, still occured on patients during hospitalization, which had a deep impact on survival and long-term outcomes. Whether these complications are due to inadequate technology and equipment of ECMO, a lack of supportive care, or simply a critical condition that might be secondary to the underlying disease in the newborn remains unclear. Further attempts, such as by improving the equipment of ECMO or increasing the use of supportive treatments like vasoactive agents, are needed to determine whether such events can be reduced.
In this study, to minimize potential bias of observational study, we established inclusion and exclusion criteria strictly to provide accurate prevalence and incidence estimation, and we limited the minimum sample size of each study to 50 to reduce publication bias. Moreover, we excluded the studies published in the ELSO database to avoid data duplication and reduce selection bias, because only the selected medical centers had the chance to register in the ELSO database, which increased selection bias. By this way, detailed VV ECMO data of other medical centers other than ELSO database were collected in this meta-analysis.