Fetal endoscopic tracheal occlusion for moderate and severe congenital diaphragmatic hernia: a systematic review and meta-analysis of randomized controlled trials

Background Fetoscopic endoluminal tracheal occlusion (FETO) is considered to increase survival among fetuses with congenital diaphragmatic hernia (CDH). Data from high-quality trials had been lacking until the largest randomized controlled trials (the TOTAL trials) were completed. This study aimed to elucidate the efficacy and safety of FETO for increasing the survival of fetuses with moderate or severe CDH. Methods Relevant studies published before August 1st, 2021 were identified by searching PubMed, Cochrane Library and Web of Science. Only randomized controlled trials (RCTs) reporting patients who underwent FETO versus patients who received standard perinatal care were included in the analysis. The primary outcome was survival in the FETO and control groups. The secondary aim was to evaluate complications during pregnancy, such as premature rupture of membranes (PROM) and preterm delivery, and neonatal complications, including the need for supplemental oxygen at birth and discharge and pulmonary hypertension in the FETO and control groups. The Mantel-Haenszel random effects model was applied, and risk ratios (RRs) or odds ratios (ORs) were calculated. Results Four RCTs were eligible for inclusion. The quality of these studies was high. The pooled estimate of survival for fetuses with moderate or severe CDH was higher in the FETO group than in the control group [odds ratio (OR), 3.43; 95% confidence interval (CI), 1.12-10.48; P = 0.03] with relatively strong evidence of between-study heterogeneity (I-2 = 66%). Subgroup analysis revealed that in the severe CDH group, the pooled estimates of neonatal survival were significantly higher in the FETO group than in the control group (OR, 6.57; 95% CI, 1.39-31.06; P = 0.02). However, in the moderate CDH group, the pooled results of neonatal survival were only slightly higher in the FETO group than in the control group (OR, 1.65; 95% CI, 0.93-2.91; P = 0.08) and the difference was not significant. The risks of PROM and preterm delivery were both higher in the FETO group. No significant difference was found for the need for supplemental oxygen at birth and discharge or in pulmonary hypertension between the FETO group and matched controls. A limitation is that we were unable to calculate the effect of the second intervention on prematurity, which would have been meaningful for evaluating the risk of FETO for PROM or preterm delivery. Conclusion FETO increases the survival rate in fetuses with moderate and severe CDH, especially in fetuses with severe CDH. However, FETO is associated with a higher risk of PROM and preterm delivery, and the optimal time of FETO should be carefully chosen.