Clinical value of screening prenatal ultrasound combined with chromosomal microarrays in prenatal diagnosis of chromosomal abnormalities

Figures & data

Figure 1. The subject selection process and relevant inclusion criteria.

Table 1. Basic data and characteristics of pregnant women.

Variables		Normal ultrasound findings	Ultrasound structural abnormalities	Isolated ultrasound anomalies	Ultrasound and CMA abnormalities
Number, N (%)		13,641 (85.80)	386 (2.4)	1877 (11.81)	381 (2.40)
Age (years)		30.52 ± 4.02	32.9 ± 4.6	32.68 ± 4.59	34.52 ± 4.78
Age >35 years		1920 (14.08)	133 (34.46)	613 (32.66)	171 (44.88)
Gestational ages (weeks)		20.01 ± 2.01	20.15 ± 2.00	21.03 ± 2.00	20.97 ± 2.04
Pregnancy history		2637 (19.33)	82 (21.24)	480 (25.57)	52 (13.65)
High-risk factors	NIST anomalies	55 (0.4)	49 (12.69)	90 (4.79)	68 (17.85)
	Trisomy 21 abnormalities	64 (0.47)	27 (6.99)	97 (5.17)	55 (14.44)
	Adverse pregnancy history	77 (0.56)	34 (8.81)	152 (8.1)	57 (14.96)
	Parental chromosomal abnormalities	15 (0.11)	18 (4.66)	51 (2.72)	29 (7.61)
	Family history of congenital malformations	24 (0.18)	6 (1.55)	28 (1.49)	31 (8.14)

Figure 2. Pictures of abnormal ultrasound result. (A) Broadening of lateral ventricle. (B) Ventricular septal defect. (C) Cleft lip and palate. (D) Dilatation of the bowel. (E) Varus foot. (F) The left ventricle exhibited hypoplasia.

Table 2. Distribution of abnormal ultrasound results.

Variables		Number	Proportion of ultrasound abnormalities (%)	Proportion of total research subjects (%)
Ultrasonographic abnormality	Simple ultrasound soft markers abnormality	1872	82.91	11.77
	Simple ultrasonographic structural abnormality	361	15.99	2.27
	Abnormal soft markers of ultrasound + abnormal structure of ultrasound	25	1.11	0.16
	Total number	2258	100.00	14.20
Simple ultrasound soft markers abnormality	2.5 mm ≤ NT < 3.0 mm	232	10.27	1.46
	3.0 mm ≤ NT < 4.0 mm	275	12.18	1.73
	NT ≥ 4.0 mm	71	3.14	0.45
	6.0 mm ≤ NF < 7.0 mm	633	28.03	3.98
	7.0 mm ≤ NF < 8.0 mm	159	7.04	1.00
	NF ≥ 8.0 mm	35	1.55	0.22
	Choroid plexus cyst	12	0.53	0.08
	Nasal bone deficiency/incomplete ossification	142	6.29	0.89
	Lateral ventricular dilation	95	4.21	0.60
	Hyperechoic bowel	49	2.17	0.31
	Single umbilical artery	28	1.24	0.18
	Renal pelvis dilation	25	1.11	0.16
	Growth restriction	36	1.59	0.23
	Others	20	0.89	0.13
	≥2 markers	60	2.66	0.38
Simple ultrasonographic structural abnormality	Cardiovascular system	127	5.62	0.80
	Nervous system	10	0.44	0.06
	Limb deformity	26	1.15	0.16
	Facial abnormalities	18	0.80	0.11
	Urinary system	55	2.44	0.35
	Digestive system	28	1.24	0.18
	Respiratory system	35	1.55	0.22
	Others	24	1.06	0.15
	≥2 systems	38	1.68	0.24

Table 3. A distribution of abnormal CMA results.

Variables		Number	Proportion of CMA abnormalities (%)	Proportion of ultrasound abnormalities (%)	Proportion of total research subjects (%)
Chromosome number abnormality	Trisomy 21	46	12.07	2.04	0.29
	Trisomy 18	11	2.89	0.49	0.07
	Sex chromosome abnormality	15	3.94	0.66	0.09
	Others	2	0.52	0.09	0.01
	Total number	74	19.42	3.28	0.47
CNVs	pCNVs	31	8.14	1.37	0.19
	Likely pCNVs	43	11.29	1.90	0.27
	VOUS CNVs	69	18.11	3.06	0.43
	Likely bCNVs	71	18.64	3.14	0.45
	bCNVs	93	24.41	4.12	0.58
	Total number	307	80.58	13.6	1.93
Total number		381	100.00	16.87	2.40

Table 4. Distribution of CMA results of pregnant women with abnormal ultrasound results.

Ultrasonographic abnormality		Number	Chromosomal abnormalities	Detection rate (%)	Chromosome number abnormality	pCNVs/likely pCNVs
Simple ultrasound soft markers abnormality	2.5 mm ≤ NT < 3.0 mm	232	11	4.74	7	4
	3.0 mm ≤ NT < 4.0 mm	275	34	12.36	18	16
	NT ≥ 4.0 mm	71	9	12.68	7	2
	6.0 mm ≤ NF < 7.0 mm	633	16	2.53	10	6
	7.0 mm ≤ NF < 8.0 mm	159	0	0.00	0	0
	NF ≥ 8.0 mm	35	1	2.86	0	1
	Choroid plexus cyst	12	0	0.00	0	0
	Nasal bone deficiency/incomplete ossification	142	9	6.34	2	7
	Lateral ventricular dilation	95	1	1.05	0	1
	Hyperechoic bowel	49	1	2.04	0	1
	Single umbilical artery	28	1	3.57	0	1
	Renal pelvis dilation	25	1	4.00	0	1
	Growth restriction	36	1	2.78	0	1
	Others	20	0	0.00	0	0
	≥2 markers	60	8	13.33	1	7
Simple ultrasonographic structural abnormality	Cardiovascular system	127	10	7.87	3	7
	Nervous system	10	0	0.00	0	0
	Limb deformity	26	0	0.00	0	0
	Facial abnormalities	18	1	5.56	1	0
	Urinary system	55	4	7.27	2	2
	Digestive system	28	0	0.00	0	0
	Respiratory system	35	0	0.00	0	0
	Others	24	10	41.67	7	3
	≥2 systems	38	18	47.37	13	5
Abnormal soft markers of ultrasound + abnormal structure of ultrasound		25	12	48.00	3	9
Total number		2258	148	6.55	74	74

Table 5. Results of CMA detection rate of NT/NF thickening under different factors.

Ultrasonographic abnormality	Amalgamative high-risk factors	Number	Chromosomal abnormalities	Detection rate (%)
NT thickening	Advanced age	49	9	18.37
	Amalgamation of bad pregnancy history	22	1	4.55
	Other abnormal soft markers of ultrasound	40	9	22.50
	No other factors are incorporated	450	40	8.89
NF thickening	Advanced age	28	1	3.57
	Amalgamation of bad pregnancy history	21	0	0.00
	Other abnormal soft markers of ultrasound	144	5	3.47
	No other factors are incorporated	715	16	2.24

Table 6. Results of univariate logistic regression analysis of fetal chromosome abnormalities.

Predictor	Univariables OR (95% CI)	p Value
Advanced age	4.17 (3.40–5.13)	<.001
Family history of congenital malformations	26.34 (16.68–41.61)	<.001
Parental chromosomal abnormalities	19.29 (12.31–30.23)	<.001
Adverse pregnancy history	11.75 (8.61–16.02)	<.001
Trisomy 21 abnormalities	16.09 (11.63–22.28)	<.001
NIST anomalies	23.03 (16.91–31.37)	<.001
Number of high risk except for advanced age	15.91 (13.02–19.42)	<.001
Number of ultrasonographic soft markers ≥2	41.28 (24.61–69.24)	<.001
Abnormal soft markers of ultrasound + abnormal structure of ultrasound	63.56 (28.36–142.42)	<.001

Table 7. Results of multivariate logistic regression analysis of fetal chromosome abnormalities.

Predictor	Multivariables OR (95% CI)	p Value
Advanced age	2.90 (2.28–3.69)	<.001
Number of high risk except for advanced age	14.28 (11.62–17.55)	<.001
Number of ultrasonographic soft markers ≥2	18.62 (10.09–34.38)	<.001
Abnormal soft markers of ultrasound + abnormal structure of ultrasound	4.86 (0.57–41.57)	.149

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.