Performance Evaluation of Noninvasive Prenatal Testing in Screening Chromosome Disorders: A Single-Center Observational Study of 15,304 Consecutive Cases in China

Figures & data

Figure 1 Flowchart of noninvasive prenatal test (NIPT) results and clinical outcome of pregnant women undergoing screening for fetal chromosome disorders between 2017 and 2022.

Abbreviations: SCA, sex-chromosomal abnormalities; CNV, copy number variant; TP, true positive; FP, false positive.

Table 1 Demographic Characteristic of Pregnant Women Undergoing Noninvasive Prenatal Testing (NIPT) for Fetal Chromosome Disorders Between 2017 and 2022

Characteristic	Total Population (n = 15,086)	High Risk (n = 2987)	Low Risk (n = 12,099)
Maternal age	28.7 ± 4.60	32.3 ± 5.29	28.2 ± 4.60
<24	2829 (18.75%)	299 (10.01)	2530 (20.91)
25–29	5781 (38.32%)	505 (16.91)	5276 (43.61)
30–34	4607 (30.54%)	314 (10.51)	4293 (35.48)
35–40	1735 (11.50%)	1735 (58.08)	0
>40	134 (0.89%)	134 (4.49)	0
GA at NIPT	18.15 ± 2.71	17.92 ± 2.14	18.21± 2.83
First trimester (≤ 13 w)	85 (0.56)	18 (0.60)	67 (0.55)
Second trimester (14–27 w)	14,855 (98.47)	2950 (98.76)	11,905 (98.40)
Third trimester (≥28 w)	102 (0.68)	10 (0.33)	92 (0.76)
Unknown	44 (0.29)	9 (0.30)	35 (0.29)
Singleton pregnancy	14,579 (96.64)	2930 (98.09)	11,649 (96.28)
Twin pregnancy	507 (3.36)	57 (1.91)	450 (3.72)
High-risk factors
Previous DS screening result
High risk	1024 (6.79)	1024 (34.28)	0
Low risk	2790 (18.49)	117 (3.92)	2673 (22.09)
No test	11,272 (74.72)	1846 (61.80)	9426 (77.91)
Other high-risk factors
Family history of aneuploidy	0	0	0
Sonographic markers of chromosomal abnormality	142 (0.94)	142 (4.75)	0
Advanced maternal age	1869 (7.40)	1869 (62.57)	0

Abbreviations: DS, Down syndrome; GA, gestational age; w, weeks.

Table 2 Pregnancy Outcomes of True Positive Cases Confirmed by Confirmatory Invasive Testing and Follow-Up Results

	Common Aneuploidy			SCA					Other Abnormalities
	T21	T18	T13	X	XXY	XYY	XXX	Deletion/ Duplication	Autosomal Trisomy	Deletion/ Duplication
Selective abortion	25	8	1	7	7	0	3	1	0	4
Pregnancy loss	0	0	0	0	0	0	0	0	0	0
Neonatal death	1	0	0	0	0	0	0	0	0	0
Term delivery	1	0	0	0	0	3	0	0	0	2

Abbreviation: SCA, sex-chromosomal abnormalities.

Table 3 Performance of Noninvasive Prenatal Testing (NIPT) in Detecting Fetal Chromosome Disorders in Pregnancies with Outcome Data

	TP (n)	FP (n)	Sensitivity (% (95% CI)	Specificity (% (95% CI)	PPV (% (95% CI)	NPV (% (95% CI)	Incidence (%)
Overall performance (n = 15,086)	65	111	100 (94.48–100)	99.27 (99.12–99.40)	38.51 (31.24–46.17)	100 (99.98–100)	0. 431
Common aneuploidy	36	19	100 (90.26–100)	99.87 (99.80–99.92)	65.45 (51.42–77.76)	100 (99.98–100)	0.239
T21	27	5	100 (87.23–100)	99.97 (99.92–99.99)	84.38 (67.21–94.72)	100 (99.98–100)	0.179
T18	8	5	100 (63.06–100)	99.97 (99.93–99.99)	61.54 (31.58–86.14)	100 (99.98–100)	0.053
T13	1	9	100 (2.50–100)	99.94 (99.89–99.97)	10.00 (0.25–44.50)	100 (99.98–100)	0.007
SCA	21	45	100 (86.28–100)	99.70 (99.60–99.78)	31.82 (20.89–44.44)	100 (99.98–100)	0.139
Other abnormalities	6	49	100 (54.07–100)	99.68 (99.57–99.76)	10.91 (4.11–22.25)	100 (99.98–100)	0.040
Theoretical PPV boundaries	–	T21 (% (n))	T18 (% (n))	T13 (% (n))	SCA (% (n))	Other abnormalities (% (n))	All abnormalities (% (n))
Lower boundary*	–	84.38 (27/32)	61.54 (8/13)	10.00 (1/10)	31.82 21/66	10.34 (6/58)	36.31 65/179
Upper boundary^#	–	84.38 (27/32)	61.54 (8/13)	10.00 (1/10)	31.82 21/66	15.52 9/58	37.99 68/179
FPR	Common aneuploidy (% (n))	T21 (% (n))	T18 (% (n))	T13 (% (n))	SCA (% (n))	Other abnormalities (% (n))	All abnormalities (% (n))
	0.13 (19/15,050)	0.03 (5/15,059)	0.03 (5/15,078)	0.06 (9/15,085)	0.27 (40/15,060)	0.32 49/15,077	0.74 111/15,018

Notes: *All unconfirmed case considered as FP; ^#All unconfirmed case considered as TP.

Abbreviations: NPV, negative predictive value; PPV, positive predictive value; FPR, false-positive rate; SCA, sex-chromosomal abnormalities; TP, true positive; FP, false positive. No false-negative cases.

Table 4 Performance of Noninvasive Prenatal Testing in Detection of Abnormalities in High-Risk Pregnancies and Low-Risk Pregnancies

NIPT Performance	High-Risk Group (n = 2987)	Low-Risk Group (n = 12,099)	P value
NIPT positive (n)	46	133	-
True positive	23	42	-
False positive	22	87	-
Lost to follow-up	1	4	-
Sensitivity (% (95% CI))	100 (85.18–100)	100 (91.59–100)	NA
Specificity (% (95% CI))	99.25 (98.88–99.53)	99.27 (99.11–99.42)	0.905
PPV (% (95% CI))	51.11 (35.77–66.30)	32.56 (24.57–41.36)	0.026
NPV (% (95% CI))	100 (99.87–100)	100 (99.97–100)	NA

Note: No false-negative cases.

Abbreviations: NIPT, noninvasive prenatal testing; PPV, positive predictive value; NPV, negative predictive value; NA, not applicable.

Table 5 Performance of Noninvasive Prenatal Testing in Detection of Abnormalities in Singleton Pregnancy and Twin Pregnancy Groups

NIPT Performance	Singleton Pregnancy Group (n = 14,579)	Twin Pregnancy Group (n = 507)	P value
NIPT positive (n)	174	5	–
True positive	66	1	–
False positive	103	4	–
Lost to follow-up	5	0	-
Sensitivity (% (95% CI))	100 (94.56–100)	100 (2.50–100)	NA
Specificity (% (95% CI))	99.29 (99.14–99.42)	99.21 (98.01–99.79)	0.7845
PPV (% (95% CI))	39.05 (31.65–46.84)	20.00 (0.51–71.64)	0.6501
NPV (% (95% CI))	100 (99.98–100)	100 (99.28–100)	NA

Notes: No false-negative cases.

Abbreviations: NIPT, noninvasive prenatal testing; PPV, positive predictive value; NPV, negative predictive value; NA, not applicable.

Table 6 Analysis of Biological Factors Causing 107 False-Positive Results

Contributing Factor	Value
Total	111
Confirmatory invasive testing	21
Follow-up	86
Maternal age (years)	29.39 (18–41)
Gestational age (weeks)	18.2 (12.6–28.1)
Live birth normal phenotype with no prenatal diagnosis
Common aneuploidy	9
SCA	39
Other abnormalities	42
Twin pregnancy	4
Fetal fraction (%)	17.56 (5.5–33.7)

Abbreviation: SCA, sex-chromosomal abnormalities.