Evaluating the effectiveness of routine noninvasive prenatal screening for CNVs in 22q11.2 region in a cohort of 38,495 pregnancies.

22q11.2 deletion syndrome (22q11.2 DS) is the second most common cause of congenital heart disease. The American College of Medical Genetics and Genomics (ACMG) has recently recommended implementing non-invasive prenatal screening (NIPS) for 22q11.2 DS for all pregnant women. This study aims to assess the effectiveness of routine NIPS for screening 22q11.2 deletion in a cohort of 38,495 pregnancies from the general population. We conducted a retrospective analysis of 38,495 pregnant women who underwent NIPS at Longgang Maternal and Child Health Hospital in Shenzhen from December 2022 to March 2024. Chromosomal microarray analysis (CMA) was performed on fetuses and pregnant women identified as high-risk for 22q11.2 DS by NIPS, using amniotic fluid samples and the leukocyte cells, respectively. Of the 38,495 cases, 22 were identified as high risk for 22q11.2 deletion by NIPS. Of these, 17 underwent amniocentesis, and 5 refused prenatal diagnosis. Concordant results between CMA and NIPS were observed in 8 cases, giving a positive predictive value (PPV) of 47.06% (8/17). Nine fetuses did not show 22q11.2 deletion by CMA, although the mothers of three fetuses were identified as having a maternal 22q11.2 deletion. Follow-up on 5 cases without prenatal diagnosis revealed one postpartum case of congenital heart disease (ventricular septal defect and atrial septal defect), three cases that were terminated, and one case that continued with normal fetal development. Routine non-invasive prenatal screening for 22q11.2 deletion demonstrates practical clinical utility and provides valuable insights for identifying pregnant women at risk for 22q11.2DS.