Comprehensive Assessment of Fetal Bilateral Ventriculomegaly Based on Genetic Disorders, Cytomegalovirus Infection, Extra Prenatal Imaging and Pregnancy Outcomes in a Tertiary Referral Center

Figures & data

Table 1 The Clinical Characteristics of 353 Pregnancies with Bilateral Ventriculomegaly

	IVM	NIVM	Total
Maternal age (Years), (Range, Median, Mean±SD)	21–41, 29, 29.0±4.4	17–40, 27, 28.2±4.4	17–41, 29, 28.5±4.4
Gestation age at VM initially detected (Range, Median, Mean±SD)	13–38, 26, 27.3±4.0	14–40, 26, 26.4±4.1	13–40, 26, 26.1±4.5
≤24 weeks (n, %)	59, 38.6	73, 36.5	133, 37.7
>24 weeks (n, %)	94, 61.4	127, 63.5	220, 62.3
Ventricular width (mm)
Mild: ≥ 10, <12 (n, %)	108, 70.6	122, 61.0	230, 65.2
Moderate: ≥ 12, <15 (n, %)	24, 15.7	44, 22.0	68, 19.2
Severe: ≥ 15 (n, %)	21, 13.7	34, 17.0	55, 15.6
Total	153	200	353

Abbreviations: BVM, bilateral ventriculomegaly; IBVM, isolated bilateral ventriculomegaly; NIBVM, non-isolated bilateral ventriculomegaly.

Table 2 Details of the Cases with Genetic Abnormalities of Clinical Significance

Case No.	Specimen	Gestational Weeks	Karyotype	CMA Results	Associated Syndrome	VM Degree	Extra Prenatal Imaging	Outcomes
1*	CB	25	46,XX,t(5;14)(p13.3;q21)	arr[hg19] Xq28(152,446,333–153,581,657)×3,1p36.33p36.23(849,466–8,592,172)×1,1q44(246,015,892–249,224,684)×3	1p36 microdeletion syndrome	Mild	None	TOP
2*	AF	24	46,XX	arr[hg19] 16p13.11(15,058,820–16,309,046)×3 pat	16p13.11 microduplication syndrome	Mild	None	Premature delivery, normal development at 3-year follow-up
3*	CB	31	46,XY	arr[hg19] 5q35.2q35.3(175,416,095–177,482,506)×1	Sotos syndrome	Mild	Echogenic intracardiac focus, EIF	TOP
4*	CB	26	46,XY	arr[hg19] 16p13.11(15,422,960–16,508,123)×1 dn	16p13.11 microdeletion syndrome	Mild	Echogenic fetal bowel	Normal development at 5-year follow-up
5	AF	24	46,XY,del(4)(p15.3)	arr[hg19] 4p16.3p15.31(68,345–20,522,754)×1	Wolf-Hirschhorn syndrome	Mild	FGR; NF thickening; persistent left superior vena cava; EIF;Single umbilical artery	TOP
6	AF	24	46,XY,der(5)t(5;9)(p13.3;p21.3)	arr[hg19] 5p15.33p13.3(113,576–32,785,953)×1, 9p24.3p21.3(208,454–21,354,180)×3	Cri-du-Chat Syndrome	Mild	Cerebellar dysplasia; thickened anterior soft tissue	TOP
7	CB	30	46,XY,-21,+mar	arr[hg19] 21q11.2q22.11(15,478,958–34,591,567)×1, 21q22.3(45,812,741–46,655,785)×1, 21q22.3(46,822,918–47,532,860)×1	None	Mild	VSD	TOP
8–10	AF	27,23,17	47,XN,+21	arr[hg19] (21)×3	Down syndrome	Mild	None	TOP
11	CB	20	47,XN,+21	arr[hg19] (21)×3	Down syndrome	Mild	Nasal bone dysplasia	TOP
12	CB	25	47,XN,+21	arr[hg19] (21)×3	Down syndrome	Mild	None	TOP
13	CB	27	46,XY,-18,+mar[13]/46,XY[47]	NA		Mild	Single umbilical artery	TOP
14	CB	33	46,XY,del(13)(q31)	NA	None	Mild	Right schizencephaly; septum pellucidum dysplasia; small cerebellar vermis; abnormal cervical thoracic spine development; left talipes; pulmonary artery stenosis	TOP
15	PB	23	47,XN,+21	NA	Down syndrome	Mild	FGR; Nasal bone dysplasia	Growth retardation mental defect at 10-month follow-up
16	CB	28	47,XY,+21	NA	Down syndrome	Mild	Short femur length	TOP
17*	CB	30	46,XY	arr[hg19] 1p36.33p36.32(849,466–4,894,800)×1, 11p15.5p15.4(230,680–8,918,951)×3	1p36 microdeletion syndrome,Silver-Russell Syndrome (SRS) or Beckwith-Wiedemann Syndrome (BWS)	Moderate	Enlarged kidneys	TOP
18	CB	25	47,XN,+21	arr[hg19] (21)×3	Down syndrome	Moderate	Severe cardiac malformation	TOP
19	PB	26	47,XN,+21	NA	Down syndrome	Moderate	Polyhydramnios; renal collecting system separating; EIF	Growth retardation mental defect at 8-month follow-up
20	AF	24	47,XY,+21	NA	Down syndrome	Moderate	FGR	TOP
21	CB	33	47,XY,+mar	NA	Unknown	Moderate	FGR	TOP
22	AF	37	47,XN,+21	NA	Down syndrome	Severe	None	TOP
23	CB	27	47,XY,+21	NA	Down syndrome	Severe	Renal collecting system separating	TOP

Note: *Additional Microdeletion/microduplication syndromes were identified by SNP-array analysis in five fetuses.

Abbreviations: VM, ventriculomegaly; CB, cord blood; AF, amniotic fluid; PB, peripheral blood; NA, not available; VSD, ventricular septal defect; NF, nuchal fold; FGR, fetal growth restriction; TOP, termination of pregnancy; EIF, echogenic intracardiac focus.

Table 3 Pregnancy Outcomes for Different Severity of Isolated Bilateral Ventriculomegaly

	Favorable Prognosis	Poor Prognosis	TOP	Total
Mild	102, 94.4%	1, 0.9%	5*, 4.6%	108
Moderate	19, 79.2%	0, 0.0%	5, 20.8%	24
Severe	1, 4.8%	2, 9.5%	18, 85.7%	21

Notes: *Chromosomal abnormalities: Four cases of trisomy 21, one case of pathogenic CNV.

Table 4 Pregnancy Outcomes of NIBVM with Different Subgroups of Prenatal Imaging

Extra Prenatal Finding	Mild				Moderate				Severe
	TOP	Favorable Prognosis	Poor Prognosis	Total	TOP	Favorable Prognosis	Poor Prognosis	Total	TOP	Favorable Prognosis	Poor Prognosis	Total
Soft marker	6, 10.3%	51, 87.9%	1, 1.7%	58	3 23.1%	8, 61.5%	2,15.4%	13	2, 100%	0, 0.0%	0, 0.0%	2
Non-structural anomaly	6, 35.3%	9, 52.9%	2, 11.8%	17	4, 50.0%	1, 12.5%	3, 37.5%	8	4, 100%	0, 0.0%	0, 0.0%	4
Structural anomaly	35, 72.9%	8, 16.7%	5, 10.4%	48	18, 81.8%	4, 18.2%	0, 0.0%	22	26, 92.9%	1, 3.6%	1,3.6%	28
Total	47, 38.2%	67, 55.3%	8, 6.5%	123	25, 58.1%	12, 30.2%	5, 11.6%	43	32, 94.1%	1, 2.9%	1, 2.9%	34

Abbreviation: TOP, termination of pregnancy.