Chromosomal analysis in pregnant women of advanced maternal age: indications for prenatal diagnosis.

The demographic of women of advanced maternal age (AMA), defined as those over 35 years, is expanding in response to the liberalization of China's three-child policy. A significant proportion of these women are electing to undergo noninvasive prenatal testing (NIPT). Nonetheless, next-generation sequencing (NGS) is the recommended method for prenatal screening among women of AMA in the world. Consequently, the decision between opting for NIPT or NGS has emerged as topic of considerable debate and interest within the medical community. The objective was to explore which prenatal screening and diagnosis is suitable for women of AMA with different comorbidities. In this retrospective study, 326 pregnant women with AMA were divided into 9 groups to investigate clinically significant copy number variation (CNV) in different amniocentesis indications by amniocentesis and NGS. Clinically significant chromosomal abnormalities were identified in 84 cases (25.8%). Among the 119 detected segmental imbalances, 16 cases (13.4%) exhibited pathogenic or likely pathogenic microdeletions or micro-duplications. The incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with soft ultrasound markers group compared to the general AMA group (11.5% vs. 1.1%; P=0.016). Additionally, the incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with NIPT group compared to the general AMA group (48.7% vs. 1.1%; P<0.001). The incorporation of soft ultrasound markers and NIPT significantly enhanced the detection rate of clinically significant CNVs in women of AMA by 10.4% and 47.6%, respectively. Furthermore, the detection rate of clinically significant CNVs increased by 37% in women of AMA who underwent NIPT, when soft ultrasound markers were present. The positive predictive value of NIPT in detecting sex chromosome aneuploidy notably improved from 57.9% to 80% with the inclusion of soft ultrasound markers. Therefore, the combination of NIPT and soft ultrasound markers in women of AMA should be strongly considered and recommended for prenatal diagnosis.