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Current diagnostic methods comprise fetal ultrasound images, which are mainly limited by fetal position and technician skills. We aimed to identify reliable maternal serum lipid biomarkers to diagnose nsCLP. Eight-feature selection methods were used to assess the dysregulated lipids from untargeted lipidomics in a discovery cohort. The robust rank aggregation algorithm was applied on these selected lipids. The data were subsequently processed using 7 classification models to retrieve a panel of 35 candidate lipid biomarkers. Potential lipid biomarkers were evaluated using targeted lipidomics in a validation cohort. Seven classification models and multivariate analyses were constructed to identify the lipid biomarkers for nsCLP. The diagnostic model achieved high performance with 3 lipids in determining nsCLP. A panel of 3 lipid biomarkers showed great potential for nsCLP diagnosis. 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