[Consensus on method selection, experimental testing, and data analysis of newborn genetic screening (2026 Edition)].

High-throughput sequencing is a revolutionary technology in newborn screening following tandem mass spectrometry. However, there is a lack of consensus regarding technical choices for laboratory implementation, detection procedures, and data analysis. This consensus document was developed through joint discussions by experts in newborn genetic screening, incorporating clinical experience and referencing the latest research. It provides recommendations covering five aspects: high-throughput sequencing method selection, experimental protocols, bioinformatics analysis strategies, data interpretation and reporting, and quality control. It is recommended to use hybrid capture gene panels as the preferred method for newborn genetic screening and experimental protocols suitable for dried blood spots. For bioinformatics analysis, a genotype-driven strategy is recommended for variant filtering. Laboratories with appropriate capabilities may combine this with a phenotype-driven strategy. Data interpretation and reporting should prioritize pathogenic or likely pathogenic variants. For diseases detectable through biochemical screening or alternative methods during the newborn period, laboratories may extend reporting to include variants of uncertain significance based on inheritance patterns and a Bayesian model score of 4 ~ 5. To align with anticipated screening outcomes (positive, uncertain, negative), reports are recommended to be categorized into primary findings (associated with disease risk) and secondary findings (such as carrier status). The performance of genetic screening protocol should assess key metrics such as analytical sensitivity.