Correlation analysis between maternal age and pathogenic copy number variations in prenatal diagnosis.

Objective This study aims to investigate the correlation between maternal age and pathogenic copy number variations (pCNVs) in prenatal diagnosis.Method A retrospective study was conducted on 17,508 cases undergoing invasive prenatal diagnosis at Longgang District Maternal and Child Health Care Hospital, Shenzhen, from June 2012 to April 2025.Stratified by maternal age, the results from both chromosomal karyotype analysis and chromosomal microarray analysis (CMA) were retrospectively analyzed. The correlation between maternal age and chromosomal abnormalities/pathogenic copy number variations was analyzed by binary logistic regression.Results In 17,508 prenatal samples, karyotyping was performed in 17,338 cases, which showed chromosome anomalies in 1,352 cases (7.80%,1,352/17,338). CMA was performed in 2,521 cases, which detected chromosomal abnormalities in 323 cases (12.81%,323/2,521) ,including 125 pathogenic copy number variations(4.96%, 125/2,521). The detection rate of CMA was significantly higher than that of karyotyping (P=0.000, X2=143.437). In this study, Karyotyping and CMA were both performed in 2,340 cases, which showed a 4.36% (102/2,340) increase in chromosome anomalies detected by CMA compared with karyotyping. By regression analysis, the incidence of Chromosomal abnormalities increased significantly with the increase of the maternal age (P=0.000; Exp (B) =1.055; CI 95% 1.048-1.062). However, the proportion of pCNVs decreased greatly(P=0.000; Exp (B) =0.947; CI 95% 0.921-0.974).Conclusion With increasing maternal age,the incidence of fetal chromosomal abnormalities,especially aneuploidies, sharply increases.Pathogenic copy number variations (pCNVs) demonstrate a negative correlation with maternal age.