Comparison of Chromosomal Microarray Analysis and Noninvasive Prenatal Testing in Pregnant Women with Fetal Ultrasonic Soft Markers

Figures & data

Table 1 The Demographic Characteristics of 539 Patients

	NIPT (n=418)	Invasive Prenatal Diagnosis (n=121)	t /χ^2	p
Maternal age at delivery (years)	29.83±5.17	31.24±5.18	2.64	0.80
Gestational week at performing	17.24±4.04	20.12±3.33	7.17	0.001
Gravidity*	2(1~6)	2(1~8)	2.04	0.15
Parity*	1(0–3)	1(0~3)	3.04	0.08

Note: *Non normal distribution; the median (minimum~maximum) was used.

Figure 1 Flow diagram illustrating the study population.

Abbreviation: NIPT, Non-invasive Prenatal Testing.

Table 2 Phenotypic Characteristics of 539 Pregnancies with Ultrasonic Soft Markers

Classification of Fetuses with Ultrasonic Soft Markers	Number of Pregnancies	NIPT	Amniocentesis /Cordocentesis
Single ultrasonic soft marker	507	403	104
Thickened nuchal translucency	35	19	16
Ventriculomegaly	11	9	2
Absent nasal bone	10	6	4
Echogenic bowel	12	8	4
Choroid plexus cyst	183	131	52
Echogenic intracardiac focus	242	217	25
Single umbilical artery	14	13	1
Two or more ultrasonic soft markers	32	15	17

Table 3 Summary of Chromosomal Aberrations in 539 Fetuses with Soft Markers

USM	Examine Type	n	Abnormal Results by CMA			High Risk of NIPT(n)	Karyotyping Undetectable, n
			Aneuploidies	P/lpCNVs	VOUS
Total	NIPT	418	9	0	0	14	0
	AC/PUBS	121	8	3	3	/	6
SUSM	NIPT	403	9	0	0	14	0
	AC/PUBS	104	6	2	3	/	5
TNT	NIPT	19	5	0	0	5	0
	AC/PUBS	16	2	1	1	/	2
VM	NIPT	9	0	0	0	0	0
	AC/PUBS	2	0	0	0	/	0
A/HNB	NIPT	6	0	0	0	0	0
	AC/PUBS	4	0	0	0	/	0
FEB	NIPT	8	0	0	0	0	0
	AC/PUBS	4	0	0	0	/	0
CPC	NIPT	131	4	0	0	7	0
	AC/PUBS	53	4	1	2	/	3
EICF	NIPT	217	0	0	0	2	0
	AC/PUBS	25	0	0	0	/	0
SUA	NIPT	13	0	0	0	0	0
	AC/PUBS	1	0	0	0	/	0
MUSM	NIPT	15	0	0	0	0	0
	AC/PUBS	17	2	0	1	/	1

Abbreviations: NIPT, noninvasive prenatal testing; CMA, chromosomal microarray analysis; AC, amniocentesis; PUBS, percutaneous umbilical blood sampling; USM, ultrasonic soft markers; SUSM, single ultrasonic soft markers; TNT, thickened nuchal translucency; VM, ventriculomegaly; A/HNB, absent/hypoplastic nasal bone; FEB, fetal echogenic bowel; CPC, choroid plexus cyst; EICF, echogenic intracardiac focus; SUA, single umbilical artery; MUSM, multiple ultrasonic soft markers; VOUS, variant of unknown significance; p/lpCNVs, pathogenic /likely pathogenic copy number variations.

Figure 2 Comparative flow diagram of the NIPT Group and the invasive prenatal diagnosis Group.

Abbreviation: NIPT, Non-invasive Prenatal Testing.

Table 4 Abnormalities Detected and Clinically Relevant Characteristics in Fetuses with Ultrasonic Soft Markers

Case	Indication	NIPT	Karyotype	CMA Results	Type of Aberration/Size Mb	Interpretation	Outcome
Case1	CPC	SCA high risk	47, XXY	arr(X)*2,(Y)*1	Aneuploidy	Path	TP
Case2	CPC	SCA high risk	45,X[10]/46,XY[40]	arr(X)*1,(Y)*0-1	Mosaicism	Path	TP
Case3	CPC	Trisomy-18 high risk	47, XN, +18	arr(18)*3	Aneuploidy	Path	TP
Case4	CPC	Trisomy-18 high risk	47, XN, +18	arr(18)*3	Aneuploidy	Path	TP
Case5	CPC	/	47, XN, +18	arr(18)*3	Aneuploidy	Path	TP
Case6	CPC	/	47, XN, +18	arr(18)*3	Aneuploidy	Path	TP
Case7	CPC	/	47, XN, +18	arr(18)*3	Aneuploidy	Path	TP
Case8	CPC	/	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case9	CPC	/	46, XN	arr[hg19]16p12.2(21,405,327–21,816,543)*1	Del/0.40	VOUS	TP
Case10	CPC	/	46, XN	arr[hg19]16p12.2(21,740,199–22,442,007)*1	Del/0.69	Likely Path	TP
Case11	CPC	/	46,XN,inv(9)(p12q13)	arr(1–22)*2,(XN)*1	Inversion	Benign	TD
Case12	CPC	/	46, XN	arr[hg19]3q21.2q23(125169451_140165851)*2hmz	LOH/15	VOUS	TD
Case13	TNT	Trisomy-21 high risk	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case14	TNT	Trisomy-21 high risk	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case15	TNT	Trisomy-21 high risk	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case16	TNT	Trisomy-21 high risk	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case17	TNT	SCA high risk	45, X	arr(1–22)*2,(X)*1	Aneuploidy	Path	TP
Case18	TNT	/	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case19	TNT	/	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case20	TNT	/	46, XN	arr[hg19]16p11.2(29,591,326–30,176,508)*1	Del/0.57	Path	TD
Case21	TNT	/	46, XN	arr[hg19]2q13(110,873,834–110,980,295)*1	Del/0.10	VOUS	TD
Case22	CPC & SUA	/	47, XN, +18	arr(18)*3	Aneuploidy	Path	TP
Case23	TNT & EB	/	47, XN, +21	arr(21)*3	Aneuploidy	Path	TP
Case24	TNT & EB	/	46, XN	arr[hg19]4q35.2(187,933,401–188,952,188)*3	Dup/1.02	VOUS	TP

Abbreviations: NIPT, noninvasive prenatal testing; CMA, chromosomal microarray analysis; TD, term delivery; TP, termination of pregnancy; SCA, sex chromosome aneuploidy; Path, pathogenic; VOUS, variant of unknown significance; Del, deletion; Dup, duplication; LOH, loss of heterozygosity; CPC, choroid plexus cyst; TNT, thickened nuchal translucency; SUA, single umbilical artery; FEB, fetal echogenic bowel.

Table 5 Chromosomal Aberrations with Ultrasonic Soft Markers in Advanced Maternal Age

Age	n	Aneuploidies			pCNV(n)	Abnormal Results(%)
		n	Pattern	Indication
≥35	118	1	Trisomy-21	CPC	0	5.08
		3	Trisomy-21	TNT
		2	Trisomy-18	CPC
≥38	47	1	Trisomy-21	CPC	0	10.64
		2	Trisomy-21	TNT
		2	Trisomy-18	CPC
≥40	26	1	Trisomy-21	CPC	0	11.54
		1	Trisomy-21	TNT
		1	Trisomy-18	CPC

Abbreviations: CPC, choroid plexus cyst; TNT, thickened nuchal translucency; pCNVs, pathogenic copy number variations.