Utility of prenatal trio whole-exome sequencing and methylation-specific multiplex ligation-dependent probe amplification in the evaluation of fetal growth restriction

Objective This study aimed to explore the application value of prenatal trio whole-exome sequencing (trio-WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in fetal growth restriction (FGR). Methods The clinical data of 66 cases of FGR in fetuses who underwent interventional prenatal diagnosis at Wenzhou Central Hospital from January 2022 to July 2025 were retrospectively collected. All fetuses had undergone chromosomal karyotype and CMA tests with negative results, and then, trio-WES was performed. Among the 21 cases with negative trio-WES results, MS-MLPA testing was further conducted. The χ 2 test was used to analyze the abnormal rates of FGR across different groups. Results In 66 cases of FGR, trio-WES could detect an additional 42.42% (28/66) of the abnormalities, among which likely pathogenic (LP)/pathogenic (P) was 27.27% (18/66). MS-MLPA detected two cases of abnormal methylation, with an abnormality rate of 9.52% (2/21). Conclusion Trio-WES and MS-MLPA can improve the detection rate of genetic abnormalities in FGR. Trio-WES and MS-MLPA are recommended as further testing methods for FGR cases with negative CMA results.