Cell-free DNA analysis in maternal blood: comparing genome-wide versus targeted approach as a first-line screening test

Figures & data

Figure 1. Flowchart of the study data.

Table 1. Summary of study population characteristics.

	Median [IQR] or N (%)
	Harmony (N = 3114)	HB-cfDNA (N = 3373)	p Value
Mother’s age (years)	30.7 [26.6–34.9]	31.0 [26.7–35.4]	.165
Mother’s weight (kg)	68 [59–78]	67 [59–77]	.170
GA in weeks	13.1 [12.4–14.3]	13.3 [12.7–14.5]	<.001
IVF	43 (1.4)	80 (2.4)	.005
Twins	72 (2.3)	64 (1.9)	.281
Common trisomies	25 (0.8)	23 (0.7)	.672

HB-cfDNA test: Home brew cfDNA test.

IQR: interquartile range.

GA: gestational age.

IVF: in vitro fertilization.

Table 2. Women’s characteristics and cell-free DNA testing failure rates obtained before and after matching of populations from both laboratories, using the propensity score.

Variables	Before matching			After matching
	Harmony (n = 3114)	HB-cfDNA (n = 3373)	ASD	Harmony (n = 3114)	HB-cfDNA (n = 3373)	ASD
Mother’s age (years)	30.80 (5.68)	30.93 (6.00)	2.18%	30.86 (5.71)	30.86 (5.99)	0.00%
GA (weeks)	14.29 (3.48)	14.44 (3.35)	4.39%	14.38 (3.61)	14.38 (3.61)	0.01%
Mother’s weight (kg)	69.69 (14.85)	69.07 (14.48)	4.24%	69.36 (14.70)	69.37 (14.62)	0.07%
IVF	1.38%	2.37%	7.31%	1.89%	1.90%	0.10%
Twins	2.31%	1.90%	2.89%	2.12%	2.11%	0.10%
Common trisomies	0.80%	0.68%	1.41%	0.73%	0.73%	0.00%
Test failure				2.81%	12.43%	<.001^a

ASD: absolute standardized difference.

GA: gestational age.

IVF: in vitro fertilization.

^a Adjusted p-value.

Table 3. Performance of the cfDNA test in the two different laboratories.

Status	Harmony (n = 3114)		HB-cfDNA (n = 3373)
	Karyotype	Detection rate	Karyotype	Detection rate
Trisomy 21	17	17 (100.0%)	18	17^a (94.4%)
Trisomy 18	7	5^b	2	2
Trisomy 13	1	1	3	2^£
Normal for T21/18 or 13	3089		3350
No result after first attempt	90		413
No result after second attempt	10 out of 61		110 out of 379
False-positive results	4 (0.1%)		1 (0.06%)

^a 1 no-call.

^b 2 no-call.

^£ 1 no-call.

Table 4. Details of the all cases with rare incidental findings on NIPT in this study.

Case #	Results NIPT	Fetal array CGH	Maternal array CGH	Ultrasound follow-up	Outcome
	Rare autosomal trisomies
2	Trisomy 16	Normal amniocentesis	Not performed	Normal	Live birth 34 wks and 2 d; Placenta shows mosaic Trisomy 16; normal follow-up
3	Trisomy 16	Normal amniocentesis	Not performed	Normal	Live birth 39 wks and 2 d; normal follow-up
10	Trisomy 7	Normal amniocentesis	Not performed	Normal	Live birth 34 wks and 2 d; normal follow-up
14	Trisomy 14	Normal amniocentesis	Not performed	Normal	Live birth 38 wks and 4 d; normal follow-up
15	Trisomy 8	Normal amniocentesis and cord blood	Not performed	Normal	Live birth 40 wks and 4 d; normal follow-up
27	Trisomy 7	Normal amniocentesis	Not performed	Normal	Live birth 37 wks and 6 d; normal follow-up
	Rare autosomal monosomy
25	Monosomy 18	Normal amniocentesis	Normal	Normal	Live birth 38 wks and 6 d: normal follow-up
	Sex chromosome aneuploidy
4	Mosaic 46XX/45X	No amniocentesis; Postnatal normal	Mother has 8–18% mosaic × 0	Normal	Live birth 39 wks and 2 d: normal follow-up
9	Mosaic 46XX/45X	No amniocentesis; Postnatal normal	Mother is mosaic × 0	Normal	Live birth 39 wks and 6 d; normal follow-up
13	Monosomy X	No amniocentesis; Postnatal normal	Normal	Normal	Live birth 39 wks and 1 d; normal follow-up
28	Mosaic 46XX/45X	No amniocentesis; Postnatal normal	Mother is mosaic × 0	Normal	Live birth 36 wks and 1 d; normal follow-up
	Large or submicroscopic partial imbalances
1	Microdeletion Xp22.31	No amniocentesis; postnatal normal	Mother carries the microdeletion	Normal	Live birth 40 wks and 2 d; normal follow-up
5	Microdeletion 13q12.11	No amniocentesis; postnatal normal	Normal	Normal	Live birth 38 wks and 0 d; normal follow-up
6	Duplication Xq22.2	No amniocentesis; postnatal normal	Mother carries duplication	Normal	Live birth 39 wks and 4 d; normal follow-up
7	Microduplication 1q21.1q21.2	No amniocentesis; postnatal follow-up finds another nonpathologic variant	Normal	Normal	Live birth 40 wks and 2 d; normal follow-up
8	Deletion Xq28	Normal amniocentesis for fetus	Mother carries deletion Xq28	Normal	Live birth 40 wks and 4 d; normal follow-up
11	Microduplication 1q21.1 1q21.2	No amniocentesis; postnatal normal	Mother carries duplication 1q21	Normal	Live birth 40 wks and 2 d; normal follow-up
12	Deletion 16p11.2	No amniocentesis; postnatal normal	Mother carries deletion 16p11.2	Normal	Live birth 37 wks and 3 d; normal follow-up
16	Microdeletion 16p11.2	No amniocentesis; postnatal normal	Mother carries deletion 16p11.2	Borderline unilateral ventriculomegaly	Live birth 40 wks and 0 d; normal follow-up
17	Microdeletion Xp.22.31	No amniocentesis; postnatal normal	Mother carries deletion X p22.31	Normal	Live birth 38 wks and 1 d; normal follow-up
18	Microdeletion X p22.31	Normal amniocentesis	Mother carries deletion X p22.31	Normal	Live birth 41 wks and 0 d; normal follow-up
19	Microduplication Xq22.1q22.2	No amniocentesis; postnatal normal	Mother carries deletion Microduplication Xq22.1q22.2	Normal	Live birth 35 wks and 6 d; normal follow-up
20	Deletion Xq	Normal amniocentesis	Normal	Normal	Live birth 38 wks and 3 d; normal follow-up
21	Microdeletion Xp21.1	No amniocentesis; postnatal normal	Mother carries deletion Xp21.1	Moderate hydronephrosis	Live birth 40 wks and 6 d; normal follow-up
22	Microduplication 1q21.1q21.2	No amniocentesis; postnatal shows child have the microduplication 1q21.1q21.2	Mother carries microduplication 1q21.1q21.2	Normal	Live birth 39 wks and 6 d; normal follow-up
23	Deletion 10q25.2q26.3	No amniocentesis; postnatal normal	Mother carries deletion 10q25.2q26.3	Normal	Live birth 41 wks and 3 d; normal follow-up
24	Deletion Xp21.1	No amniocentesis; postnatal shows child have the deletion Xp21.1	Mother carries deletion Xp21.1	Normal	Live birth 38 wks and 1 d; normal follow-up
26	Duplication long arm chromosome 8	Amniocentesis shows deletion rather than duplication	Normal	Normal	Live birth 38 wks and 1 d; normal follow-up

NIPT: Noninvasive prenatal test; CGH: comparative genomic hybridization; wks: weeks; d: days.