Abstract: Background Over the past two decades, implementing perioperative feeding protocols in infants with critical congenital heart disease (CCHD) has a certain effect on fostering their physical development and enhancing their clinical outcomes. Nevertheless, the existence of diverse feeding protocols and their appropriate application to different infant populations and feeding stages remains a pending issue. Objective To evaluate the effect of standardized perioperative feeding protocols on the physical development and clinical outcomes of critically ill infants with CCHD. Design Systematic review and meta-analysis. Methods Systematic retrieval was conducted across foreign language databases, including PubMed, Embase, The Cochrane Library, and Web of Science, as well as Chinese databases, such as SinoMed, China National Knowledge Infrastructure, and Wanfang Database. CCHD infants adhering to a standardized feeding protocol during the perioperative period were included. The outcomes evaluated included the incidence of necrotizing enterocolitis (NEC), physical development indicators, hospital length of stay (LOS), ICU LOS and mechanical ventilation duration. The study type consisted of randomized controlled trial (RCT), non-randomized trial, cohort study, case series report, and systematic review/meta-analysis. The literature was searched from the inception of the database up to December 11, 2022. Three individuals conducted literature screening and data extraction based on the predefined criteria. The risk of bias assessment for non-randomized studies and randomized clinical trials was performed using ROBINS-I and ROB 2, respectively. Meta-analysis was carried out using RevMan 5.4 and R version 4.2.2. Main outcome measures The incidence of NEC. Results A total of 11 studies conducted in the US from 2000 to 2020 were included. One article employed a non-randomized control trial, 9 used case before-after study design, and 1 used self-before-after study design. The standardized feeding protocol was implemented in 3 studies during the pre-operation period, 4 during the post-operation period, and 5 during the perioperative period. The gestational age of participants ranged from 35 to 41 weeks. Among the included articles, 8 reported the incidence of NEC as the primary outcome. Separate meta-analyses were conducted by different stages of intervention implementation. In a meta-analysis of two articles that implemented standardized protocols during the peri-operation period, the result revealed that there was no statistically significant difference in the incidence of NEC between the two groups［odds ratio (OR)=0.57 (95% CI: 0.19-1.76)］. The results of the other 2 meta-analyses were as follows: one for 3 articles implementing intervention during the pre-operation period showed no statistically significant difference［OR=0.95 (95% CI: 0.48-1.88)］ , and the other for 3 articles during the post-operation also showed no statistically significant difference［OR=0.69 (95% CI: 0.35-1.34)］. Among the 4 articles that reported the weight-for-age z-score at discharge, a meta-analysis of 3 of them found no statistically significant difference between the two groups, WMD=-0.10 (95% CI: -0.37- 0.17). Ten articles reported LOS. A meta-analysis of LOS for intervention during the pre-operation period revealed that LOS was significantly shorter in the study group, WMD=-6.83 (95% CI: -12.13--1.53). However, other meta-analyses of ICU LOS (2 articles) and mechanical ventilation duration (3 articles) all revealed no statistically significant differences between the two groups. The critical appraisal of the included articles indicated that 4 of them were at moderate risk of bias, 6 were at high risk, and 1 was at critical risk. Conclusions A standardized perioperative feeding protocol implemented in surgical infants with CCHD can not reduce the incidence of NEC, improve the weight-for-age z-score at discharge, and cut down the LOS, ICU LOS, and mechanical ventilation duration.

Key words: Neonate, Critical congenital heart disease, Perioperative period, Preoperative, Postoperative, Standardized feeding protocol, Necrotizing enterocolitis