Background: Retrospectively analyzed the results of prenatal diagnosis and hoped to provide scientific clinical guidance of prenatal screening and diagnosis for the women in advanced maternal age (AMA). Methods: In total, 4,224 women of AMA who accepted prenatal diagnosis by amniocentesis (AC) from two prenatal diagnosis centers were recruited for this study. After genetic counseling and informed consent, 3,475 women received karyotype analysis only, 703 were examined by both karyotype analysis and chromosomal microarray (CMA), while 46 cases selected CMA only. Both centers used the same detection platform, experimental scheme, and quality control standards. Results: A total of 164 women with chromosomal abnormal results were found, the abnormality rate was 3.88% (164/4,224). Among them, 145 (3.4%, 145/4,224) cases were detected as abnormal chromosome number, 19 cases (0.4%, 19/4,224) as abnormal chromosome structure. Compared with simple AMA women, the abnormality rate was significantly increased in the AMA women who combined with other indications, particularly in number abnormalities (22.5% vs. 1.0%, P<0.001). Forty-eight copy number variations (CNVs) were detected, moreover 10 cases (0.24%, 10/4,224) were proved as pathogenic or likely pathogenic CNVs. With the CMA technology, the rate of additional abnormalities with clinical significance was 1.42% (10/703). Chromosome number abnormalities significantly increased with age (P<0.001), while there were no such trends in chromosomal structural abnormalities (P=0.624). Conclusions: About 3.88% fetuses of AMA women had chromosomal abnormalities, the abnormality rate increased with their age. The application of CMA could increase the diagnostic rate by about 1.4% for AMA women, and greatly reduce their tension.

Objective To explore the impact of maternal sex chromosome aneuploidies (SCAs) and copy number variation (CNV) on false‐positive results of non‐invasive prenatal screening (NIPS) for predicting foetal SCAs. Methods In total, 22 844 pregnant women were recruited to undergo NIPS. Pregnant women with high‐risk of SCAs underwent prenatal diagnosis and maternal copy number variation sequencing (CNV‐seq). Results Among 117 women with high‐risk of SCAs, 72 accepted prenatal diagnosis, 86 accepted maternal CNV‐seq, and 21 had maternal sex chromosome abnormalities. The abnormality rate was significantly higher than women at low‐risk of SCAs (24.42% vs 3.51%). Using a novel parameter cffDNA (ChrX)/cffDNA, when the ratio was greater than 2, all foetuses had normal karyotype, and 75.0% (6/8) had abnormal maternal chromosome X. If the ratio was less than or equal to 2, only 10% (4/40) of the mothers had chromosome X CNV alterations, while 33.3% (13/40) of their foetuses had sex chromosomes CNV abnormalities. Conclusions Approximately 25% of pregnant women with SCAs predicted by NIPS had sex chromosome abnormalities as determined by CNV‐seq. The ratio of cffDNA (ChrX)/cffDNA can tentatively distinguish the maternal or foetal origin of abnormal cell‐free DNA. In a reanalysis of previous NIPS data, false‐positive results caused by maternal CNV might be elucidated.

Purpose This study aimed to explore the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal isolated nasal bone absence (INBA) or isolated nasal bone hypoplasia (INBH). We hope to provide additional relevant information for clinical counseling. Patients and Methods From November 1, 2018, to March 1, 2020, 55 pregnant women with isolated nasal bone dysplasia were admitted to the Changzhou Maternity and Child Health Care Hospital. Based on the degree of abnormality, the patients were divided into two groups: INBA and INBH. CMA was performed on all patients. The clinical data and prenatal genetic diagnoses of the two groups were retrospectively analyzed. According to the requirements of WES for samples, 12 cases with negative CMA results were selected for the WES test. Results A total of 55 cases with INBA or INBH met the inclusion criteria. In 35INBA fetuses, there was one case of trisomy 21 and one case of 10q11.22 deletion (5.7Mb), and the abnormality rate was 5.71% (2/35). Compared with INBA fetuses, the abnormality rate was increased in the fetuses with INBH [15.00% (3/20)] (15.00% vs 5.71%); there was one case of 1q21.1 duplication (1.3Mb), one case of Xp22.31 duplication (1.67Mb), and one case of 4p deletion (7.6Mb). In a later retrospective study, two pathogenic variants were identified in two cases after the WES test; the abnormality rate was 16.67% (2/12), which involved RUNX2 and CDH4 genes, respectively. Conclusion A preliminary study confirmed that molecular prenatal diagnosis should be performed in fetuses with INBA or INBH. CMA followed by WES is an effective method.

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