Application value of non-invasive prenatal testing for fetal sex chromosome aneuploidy

doi:10.3877/cma.j.issn.1673-5250.2020.05.012

Objective

To investigate the application value of non-invasive prenatal testing (NIPT) for fetal sex chromosome aneuploidy (SCA).

Methods

A total of 7 144 pregnant women who underwent NIPT in Xuzhou Maternal and Child Health Care Hospital from April 2018 to September 2019 were selected into this study. The maternal peripheral blood (5 mL) were collected for genome-wide parallel sequencing to predict the risk value of fetal SCA. Then, amniocentesis was further performed on those who showed fetal SCA by NIPT. This study was approved by the Ethics Committee of Xuzhou Maternal and Child Health Care Hospital[Approval No. 2019 (05)], and clinical research informed consent was signed with each patient.

Results

① Among 7 144 pregnant women, 27 cases (0.4%) showed fetal SCA by NIPT, of which 13 cases (48.1%) had fetal karyotype of 45, X, 6 cases (22.2%) were 47, XXX, 5 cases (18.5%) were 47, XYY, 3 cases (11.1%) were 47, XXY. ② Among 27 pregnant women with SCA, 21 underwent amniocentesis for fetal karyotype analysis. Among them, 12 cases showed no abnormality, and the other 9 cases were consistent with NIPT results. The incidence of SCA was 0.16%, and the positive predictive value of SCA was 42.8% (9/21). Among them, 3 cases were 47, XXX, and 3 cases were 47, XYY, 2 cases were 47, XXY, and 1 case was 45, X. ③ Twenty-one patients underwent amniocentesis because of abnormal NIPT results. The positive predictive values of 45, X, 47, XXX, 47, XXY and 47, XYY were 10.0%(1/10), 75.0%(3/4), 67.0%(2/3) and 75.0%(3/4), respectively; the false positive rates were 90.0%(9/10), 25.0%(1/4), 33.0%(1/3) and 25.0%(1/4), respectively. ④ After further amniocentesis, pregnant women with fetal karyotype 47, XNN showed that the median age of parents with true positive was 37 years old, which was higher than that of parents with false positive (30 years old).

Conclusion

NIPT could be a potential method for SCA screening, while this technique needed to be further investigated.

Key words: Sex chromosome aberrations, Non-invasive prenatal testing, Sex chromosomal aneuploidy, Prenatal diagnosis, Amniocentesis, Maternal age, Paternal age, Pregnant women

表1 21例NIPT结果提示胎儿SCA孕妇进一步接受羊水穿刺术检查结果(例)

SCA核型	NIPT结果为SCA呈阳性孕妇例数	羊水穿刺术检查结果
SCA核型	NIPT结果为SCA呈阳性孕妇例数	接受羊水穿刺术孕妇例数	和NIPT结果一致	正常
45，X	13	10	1(45，X)	9(46，XN)
47，XXX	6	4	3(47，XXX)	1(46，XN)
47，XXY	3	3	2(47，XXY)	1(46，XN)
47，XYY	5	4	3(47，XYY)	1(46，XN)

表1 21例NIPT结果提示胎儿SCA孕妇进一步接受羊水穿刺术检查结果(例)

SCA核型	NIPT结果为SCA呈阳性孕妇例数	羊水穿刺术检查结果
SCA核型	NIPT结果为SCA呈阳性孕妇例数	接受羊水穿刺术孕妇例数	和NIPT结果一致	正常
45，X	13	10	1(45，X)	9(46，XN)
47，XXX	6	4	3(47，XXX)	1(46，XN)
47，XXY	3	3	2(47，XXY)	1(46，XN)
47，XYY	5	4	3(47，XYY)	1(46，XN)

表2 NIPT提示胎儿SCA后接受羊水穿刺术孕妇及其丈夫年龄比较

NIPT提示SCA核型	例数	羊水穿刺术提示胎儿SCA为阳性者(n＝9)			羊水穿刺术提示胎儿SCA为假阳性者(n＝12)
NIPT提示SCA核型	例数	例数	孕妇年龄[岁，M(最小值～最大值)]	丈夫年龄[岁，M(最小值～最大值)]	例数	孕妇年龄[岁，M(最小值～最大值)]	丈夫年龄[岁，M(最小值～最大值)]
45，X	10	1	28^a	30^a	9	29(19～36)	29(24～40)
47，XXX	4	3	34(28～37)	36(29～37)	1	30^a	28^a
47，XXY	3	2	39(38～39)	39(38～39)	1	35^a	35^a
47，XYY	4	3	36(30～42)	40(31～42)	1	30^a	31^a
47，XNN	11	9	37(28～42)	37(29～42)	12	30(30～35)	30(28～35)

表2 NIPT提示胎儿SCA后接受羊水穿刺术孕妇及其丈夫年龄比较

NIPT提示SCA核型	例数	羊水穿刺术提示胎儿SCA为阳性者(n＝9)			羊水穿刺术提示胎儿SCA为假阳性者(n＝12)
NIPT提示SCA核型	例数	例数	孕妇年龄[岁，M(最小值～最大值)]	丈夫年龄[岁，M(最小值～最大值)]	例数	孕妇年龄[岁，M(最小值～最大值)]	丈夫年龄[岁，M(最小值～最大值)]
45，X	10	1	28^a	30^a	9	29(19～36)	29(24～40)
47，XXX	4	3	34(28～37)	36(29～37)	1	30^a	28^a
47，XXY	3	2	39(38～39)	39(38～39)	1	35^a	35^a
47，XYY	4	3	36(30～42)	40(31～42)	1	30^a	31^a
47，XNN	11	9	37(28～42)	37(29～42)	12	30(30～35)	30(28～35)

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