Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ2=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.
目的： 分析无创产前检测（NIPT）提示性染色体非整倍体（SCA）高风险胎儿的报告方式、产前诊断方法与产前诊断结果。 方法： 收集2015年1月至2022年4月因NIPT提示SCA高风险于南京大学医学院附属鼓楼医院接受遗传咨询，并进行侵入性产前诊断的单胎妊娠孕妇227例，回顾性分析产前诊断的方法及结果、比较染色体核型分析与染色体微阵列分析（CMA）结果的差异、NIPT筛查结果与产前诊断结果的对应关系。 结果： （1）277例SCA高风险孕妇的产前诊断方法包括：染色体核型分析73例；CMA检测41例；染色体核型分析和CMA同时检测163例，其中1例染色体核型分析和CMA同时检测者进行再次羊膜腔穿刺后羊水细胞荧光原位杂交（FISH）检测。侵入性产前诊断结果正常者166例（59.9%，166/277），异常结果包括45，X 1例（0.4%，1/277）、47，XXX 18例（6.5%，18/277）、47，XXY 36例（13.0%，36/277）、47，XYY 20例（7.2%，20/277）、48，XXXX 1例（0.4%，1/277）、SCA嵌合体20例（7.2%，20/277）、性染色体结构异常或大片段异常5例（1.8%，5/277），以及其他异常10例［3.6%，10/277；包括9例拷贝数变异（CNV）和1例平衡易位］；共诊断各类SCA共96例，NIPT筛查对SCA的阳性预测值（PPV）为34.7%（96/277）。（2）染色体核型分析与CMA同时检测的163例中，11例（6.7%，11/163）两种技术的检测结果不一致，包括5例SCA嵌合体、1例核型分析额外检出平衡易位、5例CMA技术额外检出CNV。（3）NIPT筛查报告结果包括“性染色体非整倍体”149例（53.8%，149/277）、“性染色体数目增多”54例（19.5%，54/277）和“性染色体或X染色体数目减少”74例（26.7%，74/277），其中“性染色体数目增多”和“性染色体或X染色体数目减少”的PPV分别为72.2%（39/54）和18.9%（14/74），两者比较，差异有统计学意义（χ2=34.56，P<0.01）。 结论： NIPT是SCA，特别是性染色体三体和SCA嵌合体的重要产前筛查方法，但PPV偏低；NIPT筛查各类SCA的假阳性率差异较大，报告提示具体的SCA类型和是否疑似母体SCA等信息将有助于指导遗传咨询和临床处理；对NIPT提示SCA高风险病例的产前诊断，可联合应用染色体核型分析、CMA和FISH等多技术平台综合分析。.