Abstract: Background：Though screening techniques for neonatal major congenital heart disease (mCHD) are becoming increasingly mature, their widespread acceptance and application still need to be built on economic factors. Currently, there are few studies related to the health economics of mCHD screening, and most of the data are from developed countries. Objective：To investigate the effectiveness and economics of mCHD screening. Design：Systematic review. Methods：The search strategy was established according to the rule of PIROS  participant for neonatal, index for pulse oximetry (POX), reference for echocardiography and surgery, outcome for neonatal mCHD, and study design for cost analysis, costeffectiveness analysis, costutility analysis, and costbenefit analysis. Web of Science, The Cochrane Library, MedLine, Embase, SinoMed, CNKI, and Wanfang Databases were searched from 2000 to April 28, 2022. By reading the title, abstract, and full text, relevant information was extracted including health economics indicators evaluation method, research perspective, cost collection range, sensitivity analysis type, discount rate, and health economics evaluation results such as the cost of saving one Life year (LYS), the cost of gaining a quality adjusted life year (QALY), the cost of avoiding a disability adjusted life year (DALY), the cost of an additional case diagnosed on time, and the incremental costeffectiveness/utility ratio(ICER). The quality of literature was evaluated by the Quality of Health Economic Studies (QHES) instrument. Main outcome measures:The cost and costeffectiveness of screening. Results：Eleven articles were included from 2007 to 2020, of which 7 were able to extract the data of POX screening, 4 were able to extract the data of clinical evaluation (CE) , and POX+CE screening, and 1 was able to extract the data of POX+MUR screening. There were 2 about social science, 9 about medical system, 4 about population, 7 about models, 1 with both direct cost and indirect cost, and 10 with only direct cost. Based on the exchange rate of USD in June 2022, the cost of POX screening is 224.5 USD, in which the labor cost is 2.537.4 USD, the cost of onetime probe is 13.422 USD, and the cost of reusable probe is 0.10.9 USD. CE screening costs 0.504.50 USD. MUR screening costs 1.302.0 USD. Echocardiography (ECHO) costs 301300 USD for screening positive cases. CEA/CUA (costeffectiveness/utility analysis) was used in 8 articles, among which 2 articles evaluated POX screening, 5 for POX+CE screening, and 1 for POX+MUR. The cost of using a probe and echocardiography was the main cost of screening without considering labor costs. POX, POX+MUR, and POX+CE have cost effectiveness. POX+MUR has cost effectiveness compared with ECHO. When ECHO+CE can detect other congenital defects, it has cost effectiveness compared with POX+CE. Conclusion：The cost of mCHD screening is mainly reflected in whether to use a onetime probe and echocardiography. POX, POX+MUR, and POX+CE have cost effectiveness. Neonatal mCHD screening is economically acceptable at different economic development levels.

Key words: Major congenital heart disease, Neonatal Screening, Economic evaluation, Cost-effectiveness analysis, Systematic review