Predictive value of single and combined detection of common prenatal screening indexes for pregnant women on fetal chromosomal abnormalities

doi:10.3877/cma.j.issn.1673-5250.2023.06.006

Objective

To investigate the predictive value of single and combined detection of common prenatal screening indexes for pregnant women on fetal chromosomal abnormalities.

Methods

From January 2018 to September 2021, a total of 1 000 cases of pregnant women who underwent amniocentesis in Affiliated Hospital of Inner Mongolia Medical University, were enrolled into this study. The clinical data were analyzed by retrospective analysis method. Binary logistic regression analysis was conducted to investigate the correlation between common prenatal screening indexes and fetal chromosomal aneuploidy. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of single and combined tests such as maternal serum screening tests, fetal ultrasonic soft indexes, noninvasive prenatal testing (NIPT) for screening fetal chromosomal abnormalities. The procedure followed in this study was approved by the Ethics Committee of our hospital (Approval No. YKD2016108). Informed concents were obtained from all participants.

Results

① The total rate of fetal chromosomal abnormalities in this study was 14.0% (140/1 000). Among them, the abnormal rates of chromosome number, chromosome structure, and other types of chromosome abnormal were 72.9%, 18.6% and 8.6%, respectively. ② The results of binary logistic regression analysis showed that maternal serum screening tests showed high risk for trisomy 21 and trisomy 18 (OR=3.030, 10.094), fetal ultrasonic soft index abnormalities, structural abnormalities (OR=6.125, 3.774), and NIPT showed high risk for trisomy 21, trisomy 18, trisomy 13 and sex chromosomal abnormalities (OR=877.846, 29.111, 37.651, 43.514) were all related to fetal chromosomal aneuploidy (P<0.05). ③ The positive predictive values of NIPT combined with advanced pregnancy, maternal serum screening tests, and fetal ultrasonic soft indexes, respectively, for screening fetal chromosomal abnormalities were 52.5% (31/59), 44.8% (13/29) and 75.0% (6/8), respectively, which were respectively higher than those of 4.7% (8/172) of advanced pregnancy alone, 5.5% (15/273) of maternal serum screening tests alone, and 10.1% (20/198) of fetal ultrasonic soft indexes alone, and the differences were statistically significant (χ²=71.80, 48.21, 23.78; all with P<0.001). ④ The analysis of ROC curve results showed that the area under curve (AUC) and sensitivity of screening fetal chromosomal abnormalities in the advanced pregnancy combined with NIPT were higher than those in the advanced pregnancy, and the differences were statistically significant (P<0.05). To the fetal ultrasonic soft indexes combined with NIPT screening for fetal chromosomal abnormalities, the AUC was higher than that of fetal ultrasonic soft indexes alone, the specificity was higher than that of NIPT alone, and the differences were statistically significant (P<0.05). There were no significant differences between maternal serum screening tests combined with NIPT and one of them alone in AUC, sensitivity and specificity (P>0.05).

Conclusions

Advanced pregnancy combined with NIPT can effectively reduce the use of interventional prenatal diagnosis. Maternal serum screening tests combined with NIPT can reduce the cost of screening fetal chromosomal abnormalities. Fetal ultrasonic soft indexes combined with NIPT has the best efficiency in diagnosing fetal chromosomal abnormalities.

Key words: Maternal serum screening tests, Ultrasonography, prenatal, Non-invasive prenatal testing, Advanced pregnancy, Aneuploidy, ROC curve, Pregnant women

表1 本组孕妇各产前筛查指标异常对胎儿染色体异常的阳性预测值[%(n/n′)]

筛查指标异常	阳性预测值	筛查指标异常	阳性预测值	筛查指标异常	阳性预测值
胎儿超声软指标	16.3(49/300)	胎儿超声胎儿结构	14.8(9/61)	NIPT	47.9(69/144)
NT增厚	21.9(32/146)	心脏畸形	18.2(6/33)	21-三体	89.7(35/39)
鼻骨发育异常	14.3(4/28)	唇(腭)裂	11.1(1/9)	18-三体	32.0(8/25)
单脐动脉	16.7(3/18)	足内翻	14.3(1/7)	13-三体	28.6(2/7)
肾盂分离	5.6(1/18)	肾脏发育异常	0(0/6)	性染色体异常	32.1(18/56)
心室强回声	7.7(1/13)	十二指肠闭锁	25.0(1/4)	染色体其他类型异常	35.3(6/17)
侧脑室增宽	18.2(2/11)	多指(趾)	0(0/2)	高龄孕妇	17.9(59/330)
脉络丛囊肿	0(0/10)	血清学筛查	9.8(36/368)	家族不良生育史	6.9(9/130)
右位主动脉弓	0(0/9)	21-三体临界风险	10.8(8/74)	夫妻一方染色体异常	26.7(12/45)
迷走右锁骨下动脉	0(0/9)	21-三体高风险	8.5(21/246)
肠管回声增强	16.7(1/6)	18-三体临界风险	25.0(3/12)
颈部水囊瘤	100.0(5/5)	18-三体高风险	5.7(4/70)

表1 本组孕妇各产前筛查指标异常对胎儿染色体异常的阳性预测值[%(n/n′)]

筛查指标异常	阳性预测值	筛查指标异常	阳性预测值	筛查指标异常	阳性预测值
胎儿超声软指标	16.3(49/300)	胎儿超声胎儿结构	14.8(9/61)	NIPT	47.9(69/144)
NT增厚	21.9(32/146)	心脏畸形	18.2(6/33)	21-三体	89.7(35/39)
鼻骨发育异常	14.3(4/28)	唇(腭)裂	11.1(1/9)	18-三体	32.0(8/25)
单脐动脉	16.7(3/18)	足内翻	14.3(1/7)	13-三体	28.6(2/7)
肾盂分离	5.6(1/18)	肾脏发育异常	0(0/6)	性染色体异常	32.1(18/56)
心室强回声	7.7(1/13)	十二指肠闭锁	25.0(1/4)	染色体其他类型异常	35.3(6/17)
侧脑室增宽	18.2(2/11)	多指(趾)	0(0/2)	高龄孕妇	17.9(59/330)
脉络丛囊肿	0(0/10)	血清学筛查	9.8(36/368)	家族不良生育史	6.9(9/130)
右位主动脉弓	0(0/9)	21-三体临界风险	10.8(8/74)	夫妻一方染色体异常	26.7(12/45)
迷走右锁骨下动脉	0(0/9)	21-三体高风险	8.5(21/246)
肠管回声增强	16.7(1/6)	18-三体临界风险	25.0(3/12)
颈部水囊瘤	100.0(5/5)	18-三体高风险	5.7(4/70)

表2 本组孕妇各产前筛查指标与胎儿染色体非整倍体关系的二元logistic回归分析结果

产前筛查指标	B	SE	Wald值	P值	OR值	OR值95%CI
高龄妊娠(vs非高龄妊娠)	0.564	0.321	3.083	0.079	1.758	0.936～3.302
血清学筛查21-三体(vs低风险)			6.700	0.082
临界风险	0.240	0.713	0.114	0.736	1.272	0.314～5.141
高风险	1.109	0.554	4.002	0.045	3.030	1.023～8.979
血清学筛查18-三体(vs低风险)			16.600	<0.001
临界风险	1.268	1.182	1.151	0.283	3.555	0.350～36.076
高风险	2.312	0.571	16.387	<0.001	10.094	3.295～30.916
胎儿超声软指标异常(vs无异常)	1.812	0.381	22.658	<0.001	6.125	2.904～12.919
胎儿超声胎儿结构异常(vs无异常)	1.328	0.526	6.376	0.012	3.774	1.346～10.579
NIPT			103.422	<0.001
21-三体高风险(vs低风险)	6.777	0.958	50.012	<0.001	877.846	134.171～5 743.507
18-三体高风险(vs低风险)	3.371	0.840	16.114	<0.001	29.111	5.613～150.973
13-三体高风险(vs低风险)	3.628	1.140	10.135	0.001	37.651	4.033～351.480
性染色体异常(vs无异常)	3.773	0.786	23.035	<0.001	43.514	9.321～203.141
染色体其他类型异常(vs无异常)	－16.707	10 216.868	0	0.999	0	0～0
家族不良生育史(vs无不良生育史)	－0.546	0.765	0.509	0.476	0.579	0.129～2.596
夫妻一方染色体异常(vs无异常)	0.049	1.141	0.002	0.966	1.050	0.112～9.828

表2 本组孕妇各产前筛查指标与胎儿染色体非整倍体关系的二元logistic回归分析结果

产前筛查指标	B	SE	Wald值	P值	OR值	OR值95%CI
高龄妊娠(vs非高龄妊娠)	0.564	0.321	3.083	0.079	1.758	0.936～3.302
血清学筛查21-三体(vs低风险)			6.700	0.082
临界风险	0.240	0.713	0.114	0.736	1.272	0.314～5.141
高风险	1.109	0.554	4.002	0.045	3.030	1.023～8.979
血清学筛查18-三体(vs低风险)			16.600	<0.001
临界风险	1.268	1.182	1.151	0.283	3.555	0.350～36.076
高风险	2.312	0.571	16.387	<0.001	10.094	3.295～30.916
胎儿超声软指标异常(vs无异常)	1.812	0.381	22.658	<0.001	6.125	2.904～12.919
胎儿超声胎儿结构异常(vs无异常)	1.328	0.526	6.376	0.012	3.774	1.346～10.579
NIPT			103.422	<0.001
21-三体高风险(vs低风险)	6.777	0.958	50.012	<0.001	877.846	134.171～5 743.507
18-三体高风险(vs低风险)	3.371	0.840	16.114	<0.001	29.111	5.613～150.973
13-三体高风险(vs低风险)	3.628	1.140	10.135	0.001	37.651	4.033～351.480
性染色体异常(vs无异常)	3.773	0.786	23.035	<0.001	43.514	9.321～203.141
染色体其他类型异常(vs无异常)	－16.707	10 216.868	0	0.999	0	0～0
家族不良生育史(vs无不良生育史)	－0.546	0.765	0.509	0.476	0.579	0.129～2.596
夫妻一方染色体异常(vs无异常)	0.049	1.141	0.002	0.966	1.050	0.112～9.828

表3 本组孕妇NIPT分别联合高龄妊娠、血清学筛查、胎儿超声软指标对胎儿染色体异常的阳性预测值[%(n/n′)]

胎儿染色体异常类型	NIPT联合高龄妊娠筛查	NIPT联合血清学筛查	NIPT联合胎儿超声软指标筛查
21-三体	92.9(13/14)	88.9(8/9)	80.0(4/5)
18-三体	35.7(5/14)	20.0(1/5)	0(0/2)
13-三体	33.3(1/3)	50.0(1/2)	0/0^a
性染色体异常	39.1(9/23)	33.3(3/9)	100.0(1/1)
其他类型异常	60.0(3/5)	0(0/4)	1/0^a

表3 本组孕妇NIPT分别联合高龄妊娠、血清学筛查、胎儿超声软指标对胎儿染色体异常的阳性预测值[%(n/n′)]

胎儿染色体异常类型	NIPT联合高龄妊娠筛查	NIPT联合血清学筛查	NIPT联合胎儿超声软指标筛查
21-三体	92.9(13/14)	88.9(8/9)	80.0(4/5)
18-三体	35.7(5/14)	20.0(1/5)	0(0/2)
13-三体	33.3(1/3)	50.0(1/2)	0/0^a
性染色体异常	39.1(9/23)	33.3(3/9)	100.0(1/1)
其他类型异常	60.0(3/5)	0(0/4)	1/0^a

图1　本组孕妇高龄妊娠、NIPT单独筛查及二者联合筛查胎儿染色体异常的ROC曲线　图2　本组孕妇血清学、NIPT单独筛查及二者联合筛查胎儿染色体异常的ROC曲线　图3　本组孕妇胎儿超声软指标、NIPT单独筛查及二者联合筛查胎儿染色体异常的ROC曲线注：NIPT为无创产前检查，ROC曲线为受试者工作特征曲线

表4 本组孕妇高龄妊娠、血清学、胎儿超声软指标及NIPT单独筛查，以及NIPT分别联合上述3项筛查对胎儿染色体异常的筛查效能

筛查手段	AUC	SE	AUC 95%CI	敏感度(%)	特异度(%)
①高龄妊娠	0.350	0.074	0.205～0.496	47.1	23.0
②血清学筛查	0.495	0.073	0.352～0.637	88.2	10.7
③胎儿超声软指标	0.453	0.059	0.338～0.568	69.0	21.6
④NIPT	0.550	0.098	0.358～0.742	100.0	10.0
⑤高龄妊娠联合NIPT	0.563	0.073	0.420～0.705	100.0	12.5
⑥血清学筛查联合NIPT	0.556	0.104	0.351～0.760	100.0	11.1
⑦胎儿超声软指标联合NIPT	0.800	0.151	0.505～1.000	100.0	60.0

表4 本组孕妇高龄妊娠、血清学、胎儿超声软指标及NIPT单独筛查，以及NIPT分别联合上述3项筛查对胎儿染色体异常的筛查效能

筛查手段	AUC	SE	AUC 95%CI	敏感度(%)	特异度(%)
①高龄妊娠	0.350	0.074	0.205～0.496	47.1	23.0
②血清学筛查	0.495	0.073	0.352～0.637	88.2	10.7
③胎儿超声软指标	0.453	0.059	0.338～0.568	69.0	21.6
④NIPT	0.550	0.098	0.358～0.742	100.0	10.0
⑤高龄妊娠联合NIPT	0.563	0.073	0.420～0.705	100.0	12.5
⑥血清学筛查联合NIPT	0.556	0.104	0.351～0.760	100.0	11.1
⑦胎儿超声软指标联合NIPT	0.800	0.151	0.505～1.000	100.0	60.0

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