Ultrasonographic characteristics and prognosis of fetal congenital absent pulmonary valve syndrome

doi:10.3877/cma.j.issn.1673-5250.2023.04.006

Objective

To analyze ultrasonographic characteristics and concomitant malformations and prognosis of absent pulmonary valve syndrome (APVS).

Methods

From November 2010 to December 2020, a total of 26 fetuses (fetus 1-26) diagnosed as APVS in Beijing Anzhen Hospital, Capital Medical University were selected in the study, and they were enrolled into APVS group. Meanwhile, other 78 healthy fetuses who prenatal examination at the same hospital and fetal age match with APVS group were enrolled into control group. Fetal age at diagnosis, cardiothoracic ratio, cardiac axis, presence of combined intra- and extracardiac malformations and heart failure, ventricular septal defect (VSD) size, aortic ride-through rate, lung area, aortic valve annular diameter, pulmonary valve annular diameter, pulmonary artery trunk and branch diameter, left atrial internal diameter, left ventricular internal diameter, right atrial internal diameter, right ventricular internal diameter, aortic valve flow velocity and pulmonary valve flow velocity were collected and compared between 2 groups. Further, 4 fetuses with copy number variant sequencing (CNV-seq) results were collected. The influencing factors of fetal APVS diagnosis and identification were analyzed by multivariate unconditional logistic regression analysis. The procedure followed in this study conformed to the standards formulated by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University, and was approved by the Ethics Committee (Approval No. 2023135X). Written informed consents were obtained from pregnant mother of all fetuses.

Results

①Among 26 cases of APVS fetuses, 17 cases (17/26, 65.4%) were tetralogy of Fallot (TOF)-type APVS, 4 cases (4/26, 15.4%) were isolated APVS, and 5 cases (5/26, 19.2%) were complicated with heart malformation.② Echocardiography of 26 APVS cases showed stenosis of pulmonary valve ring, absence or dysplasia of pulmonary valve leaves, and tumor-like expansion of pulmonary trunk and left and right branches. Examination result of color doppler flow imaging(CDFI)showed severe regurgitation of fetal pulmonary valve in 26 cases, and pulsed-wave Doppler (PW) measured increased blood flow velocity of fetal pulmonary valve in 23 cases. ③Among 26 APVS fetuses, 1 case was stillborn, 18 cases were induced to terminate pregnancy, and 12 cases of 19 cases were confirmed by autopsy. One of them was misdiagnosed as pulmonary valve stenosis by fetal echocardiography. Seven cases lost follow-up. ④ There were significant differences in fetal heart axis, cardiothoracic ratio, right ventricular diameter, aortic annulus diameter, pulmonary annulus diameter, left pulmonary artery diameter, right pulmonary artery diameter, aortic valve velocity and pulmonary valve velocity between two groups (P<0.05). ⑤Multivariate unconditional logistics regression analysis showed that gestational age (OR=0.538, 95%CI: 0.295-0.984, P=0.044), right ventricular diameter (OR=2.772, 95%CI: 1.024-7.511, P=0.045), cardiac axis (OR=1.331, 95%CI: 1.101-1.608, P=0.003), and cardiothoracic ratio (OR=2.084, 95%CI: 1.082-4.017, P=0.028) were influencing factors to identify the existence of fetal APVS.

Conclusions

Fetal APVS is a rare conic malformation. Pulmonary valve absence or hypoplasia, pulmonary valve ring stenosis, pulmonary artery trunk or branch tumor-like dilation are typical ultrasound features. Combined with the parameters of cardiac axis, right ventricle and cardiothoracic ratio, it will improves the prenatal ultrasound diagnosis rate. Fetal APVS affects the development of left lung. The prenatal ultrasound diagnosis of fetal APVS provides important information for prenatal prognosis consultation and timely treatment after birth.

Key words: Absence of pulmonary valve syndrome, Echocardiography, Prenatal diagnosis, Logistic models, Fetus

表1 2组胎儿胎龄及其母亲年龄比较(±s)

组别	例数	胎龄(周)	母亲年龄(岁)
AVPS组	26	25.8±4.1	28.9±3.5
对照组	78	26.5±4.0	28.1±3.8
t值		0.75	－0.94
P值		0.457	0.350

表1 2组胎儿胎龄及其母亲年龄比较(±s)

组别	例数	胎龄(周)	母亲年龄(岁)
AVPS组	26	25.8±4.1	28.9±3.5
对照组	78	26.5±4.0	28.1±3.8
t值		0.75	－0.94
P值		0.457	0.350

表2 本研究26例APVS胎儿(胎儿1~26)胎龄、母亲年龄及主要心脏畸形比较

胎儿编号	母亲年龄(岁)	胎龄(周)	主要心脏畸形	胎儿编号	母亲年龄(岁)	胎龄(周)	主要心脏畸形
1	26	24⁺⁵	TOF	14	27	18⁺⁶	TOF
2	28	25⁺⁵	—	15	32	20⁺⁵	MA、DORV、RAA、ALSA
3	32	21⁺⁵	TOF	16	33	24	TOF、RAA
4	28	23⁺¹	TOF、RAA、ALSA	17	28	22	TAPVC、VSD、HAAO
5	29	30⁺⁶	—	18	29	23⁺¹	TOF
6	30	27	TOF	19	30	24	TOF、RAA
7	32	26⁺²	TOF	20	22	24⁺²	TOF
8	22	26	TOF	21	27	27	TOF
9	29	31⁺²	TOF	22	28	23⁺⁶	—
10	27	32⁺³	SV、RAA	23	26	36⁺⁵	VI、SV
11	35	31⁺¹	TOF	24	26	24⁺⁴	TOF、RAA
12	35	23⁺⁴	TECD、SV	25	27	23	TOF
13	29	25⁺²	TOF、ACUA	26	35	30	—

表2 本研究26例APVS胎儿(胎儿1~26)胎龄、母亲年龄及主要心脏畸形比较

胎儿编号	母亲年龄(岁)	胎龄(周)	主要心脏畸形	胎儿编号	母亲年龄(岁)	胎龄(周)	主要心脏畸形
1	26	24⁺⁵	TOF	14	27	18⁺⁶	TOF
2	28	25⁺⁵	—	15	32	20⁺⁵	MA、DORV、RAA、ALSA
3	32	21⁺⁵	TOF	16	33	24	TOF、RAA
4	28	23⁺¹	TOF、RAA、ALSA	17	28	22	TAPVC、VSD、HAAO
5	29	30⁺⁶	—	18	29	23⁺¹	TOF
6	30	27	TOF	19	30	24	TOF、RAA
7	32	26⁺²	TOF	20	22	24⁺²	TOF
8	22	26	TOF	21	27	27	TOF
9	29	31⁺²	TOF	22	28	23⁺⁶	—
10	27	32⁺³	SV、RAA	23	26	36⁺⁵	VI、SV
11	35	31⁺¹	TOF	24	26	24⁺⁴	TOF、RAA
12	35	23⁺⁴	TECD、SV	25	27	23	TOF
13	29	25⁺²	TOF、ACUA	26	35	30	—

表3 本研究APVS组26例APVS胎儿(胎儿1~26)超声心动图参数比较

胎儿编号	VSD(mm)	主动脉骑跨率(%)	心轴(°)	心胸比(%)	左心房内径(mm)	右心房内径(mm)	左心室内径(mm)	右心室内径(mm)
1	4.4	70	76.0	32	11.7	11.0	9.8	12.7
2	－	－	66.0	51	7.4	13.8	9.8	15.0
3	3.9	50	66.0	32	5.7	9.5	7.1	12.1
4	4.7	40	56.0	32	7.4	7.7	7.4	8.9
5	6.6	50	57.0	28	9.5	11.0	9.3	12.6
6	5.1	50	95.0	26	9.9	13.0	8.5	17.0
7	5.2	50	61.0	35	9.5	11.8	12.5	10.8
8	4.6	60	44.0	32	8.8	13.7	8.8	13.4
9	4.4	20	43.0	35	8.5	9.1	9.8	12.4
10	－	－	40.0	26	9.2	12.9	－	26.5
11	7.6	60	－	－	12.6	14.6	11.8	13.5
12	－	－	78.0	30	7.5	12.6	7.4	13.1
13	4.1	50	62.0	34	8.9	10.3	9.0	10.9
14	5.0	50	77.6	26	6.1	5.7	6.0	6.7
15	2.9	－	70.0	28	6.0	6.7	3.2	10.8
16	3.1	30	82.0	30	8.6	9.6	8.1	9.5
17	4.0	30	54.0	29	4.7	8.7	9.4	9.8
18	2.8	30	50.0	31	8.5	9.3	8.9	9.5
19	3.8	30	60.0	30	9.2	10.1	9.0	10.8
20	7.6	30	55.0	31	9.5	10.6	9.1	11.0
21	4.0	50	50.0	29	11.4	12.3	10.3	11.0
22	－	－	46.0	29	6.7	10.7	7.0	12.5
23	－	－	45.0	28	12.3	14.2	15.6	－
24	4.4	60	35.0	30	8.8	9.1	8.0	8.7
25	3.8	50	120.0	38	5.3	9.4	9.3	11.4
26	－	－	54.0	41	13.4	15.5	15.4	16.6
胎儿编号	主动脉瓣环径(mm)	肺动脉瓣环径(mm)	肺动脉主干径(mm)	左肺动脉内径(mm)	右肺动脉内径(mm)	动脉导管内径(mm)	主动脉瓣流速(cm/s)	肺动脉瓣流速(cm/s)
1	6.8	3.0	9.1	10.9	9.8	－	94	172
2	4.0	5.8	11.6	5.2	4.6	－	102	124
3	4.5	2.5	16.8	9.5	9.7	－	83	189
4	3.3	3.8	7.1	4.9	5.2	－	79	192
5	6.2	4.8	11.2	5.5	7.3	－	69	180
6	5.7	2.6	7.2	6.3	6.6	2.8	72	177
7	6.1	4.7	10.5	6.5	9.8	3.0	105	183
8	6.7	3.3	19.0	9.6	9.8	－	64	138
9	5.7	3.0	9.5	5.6	6.9	－	103	248
10	6.3	5.9	15.9	13.4	12.4	－	64	63
11	6.1	3.0	9.2	6.2	5.4	3.5	90	143
12	4.1	3.9	8.9	4.5	5.3	－	56	157
13	5.5	3.1	8.7	6.1	6.2	－	74	168
14	4.1	2.3	5.3	3.0	3.1	2.0	91	198
15	4.9	3.1	7.8	6.6	5.5	－	85	120
16	5.8	3.9	9.5	5.2	7.9	－	90	153
17	2.1	3.0	6.0	2.8	3.2	－	66	146
18	5.3	3.8	9.2	6.3	5.9	－	89	138
19	4.7	2.7	5.9	6.8	4.6	－	94	177
20	5.1	2.8	12.5	8.5	5.2	－	87	205
21	5.8	4.0	7.9	4.3	3.9	3.0	88	143
22	3.3	3.6	6.7	2.4	2.4	2.1	85	164
23	5.7	3.2	10.4	5.1	5.0	2.5	90	145
24	5.4	6.0	14.8	6.1	6.4	－	80	224
25	4.8	4.0	10.8/融合部20.3	22.0	16.0	2.2	91	82
26	5.8	12.6	13.8	3.2	3.7	3.1	87	63

表3 本研究APVS组26例APVS胎儿(胎儿1~26)超声心动图参数比较

胎儿编号	VSD(mm)	主动脉骑跨率(%)	心轴(°)	心胸比(%)	左心房内径(mm)	右心房内径(mm)	左心室内径(mm)	右心室内径(mm)
1	4.4	70	76.0	32	11.7	11.0	9.8	12.7
2	－	－	66.0	51	7.4	13.8	9.8	15.0
3	3.9	50	66.0	32	5.7	9.5	7.1	12.1
4	4.7	40	56.0	32	7.4	7.7	7.4	8.9
5	6.6	50	57.0	28	9.5	11.0	9.3	12.6
6	5.1	50	95.0	26	9.9	13.0	8.5	17.0
7	5.2	50	61.0	35	9.5	11.8	12.5	10.8
8	4.6	60	44.0	32	8.8	13.7	8.8	13.4
9	4.4	20	43.0	35	8.5	9.1	9.8	12.4
10	－	－	40.0	26	9.2	12.9	－	26.5
11	7.6	60	－	－	12.6	14.6	11.8	13.5
12	－	－	78.0	30	7.5	12.6	7.4	13.1
13	4.1	50	62.0	34	8.9	10.3	9.0	10.9
14	5.0	50	77.6	26	6.1	5.7	6.0	6.7
15	2.9	－	70.0	28	6.0	6.7	3.2	10.8
16	3.1	30	82.0	30	8.6	9.6	8.1	9.5
17	4.0	30	54.0	29	4.7	8.7	9.4	9.8
18	2.8	30	50.0	31	8.5	9.3	8.9	9.5
19	3.8	30	60.0	30	9.2	10.1	9.0	10.8
20	7.6	30	55.0	31	9.5	10.6	9.1	11.0
21	4.0	50	50.0	29	11.4	12.3	10.3	11.0
22	－	－	46.0	29	6.7	10.7	7.0	12.5
23	－	－	45.0	28	12.3	14.2	15.6	－
24	4.4	60	35.0	30	8.8	9.1	8.0	8.7
25	3.8	50	120.0	38	5.3	9.4	9.3	11.4
26	－	－	54.0	41	13.4	15.5	15.4	16.6
胎儿编号	主动脉瓣环径(mm)	肺动脉瓣环径(mm)	肺动脉主干径(mm)	左肺动脉内径(mm)	右肺动脉内径(mm)	动脉导管内径(mm)	主动脉瓣流速(cm/s)	肺动脉瓣流速(cm/s)
1	6.8	3.0	9.1	10.9	9.8	－	94	172
2	4.0	5.8	11.6	5.2	4.6	－	102	124
3	4.5	2.5	16.8	9.5	9.7	－	83	189
4	3.3	3.8	7.1	4.9	5.2	－	79	192
5	6.2	4.8	11.2	5.5	7.3	－	69	180
6	5.7	2.6	7.2	6.3	6.6	2.8	72	177
7	6.1	4.7	10.5	6.5	9.8	3.0	105	183
8	6.7	3.3	19.0	9.6	9.8	－	64	138
9	5.7	3.0	9.5	5.6	6.9	－	103	248
10	6.3	5.9	15.9	13.4	12.4	－	64	63
11	6.1	3.0	9.2	6.2	5.4	3.5	90	143
12	4.1	3.9	8.9	4.5	5.3	－	56	157
13	5.5	3.1	8.7	6.1	6.2	－	74	168
14	4.1	2.3	5.3	3.0	3.1	2.0	91	198
15	4.9	3.1	7.8	6.6	5.5	－	85	120
16	5.8	3.9	9.5	5.2	7.9	－	90	153
17	2.1	3.0	6.0	2.8	3.2	－	66	146
18	5.3	3.8	9.2	6.3	5.9	－	89	138
19	4.7	2.7	5.9	6.8	4.6	－	94	177
20	5.1	2.8	12.5	8.5	5.2	－	87	205
21	5.8	4.0	7.9	4.3	3.9	3.0	88	143
22	3.3	3.6	6.7	2.4	2.4	2.1	85	164
23	5.7	3.2	10.4	5.1	5.0	2.5	90	145
24	5.4	6.0	14.8	6.1	6.4	－	80	224
25	4.8	4.0	10.8/融合部20.3	22.0	16.0	2.2	91	82
26	5.8	12.6	13.8	3.2	3.7	3.1	87	63

图4 本研究APVS组胎儿13(胎龄为25⁺²周)PW测量显示肺动脉瓣上流速增快，肺动脉瓣处"穿梭"血流信号

表4 2组胎儿超声心动图检查结果比较[M(Q₁，Q₃)]

组别	例数	心轴(°)	心胸比(%)	左心房内径(mm)	右心房内径(mm)	左心室内径(mm)^a	右心室内径(mm)^a	主动脉瓣环径(mm)
APVS组	26	61.7(35.0，120.0)	31.7(26.0，51.0)	8.7(4.7，13.4)	10.9(5.7，15.5)	9.2(3.2，15.6)	12.3(6.7，26.5)	5.1(2.1，6.8)
对照组	78	35.7(25.0，51.0)	28.6(25.0，33.0)	9.7(5.7，14.8)	11.0(6.8，18.0)	9.3(5.5，16.0)	9.9(6.2，17.0)	4.3(2.8，7.5)
Z值		－6.80	－3.22	－1.84	－0.19	－0.13	－3.10	－3.62
P值		<0.001	0.001	0.065	0.851	0.894	0.002	<0.001
组别	例数	肺动脉瓣环径(mm)	左肺动脉内径(mm)	右肺动脉内径(mm)	动脉导管内径(mm)^a	主动脉瓣流速(cm/s)	肺动脉瓣流速(cm/s)
APVS组	26	4.0(2.3，12.6)	6.8(2.4，22.0)	6.6(2.4，16.0)	2.7(2.0，3.5)	83.8(56.0，105.0)	157.4(63.0，248.0)
对照组	78	5.6(2.7，9.1)	2.3(1.3，3.9)	2.4(1.3，4.5)	2.5(1.3，4.9)	66.8(41.0，108.7)	60.1(40.0，95.4)
Z值		－5.17	－7.19	－7.25	－1.28	－4.64	－7.23
P值		<0.001	<0.001	<0.001	0.202	<0.001	<0.001

表4 2组胎儿超声心动图检查结果比较[M(Q₁，Q₃)]

组别	例数	心轴(°)	心胸比(%)	左心房内径(mm)	右心房内径(mm)	左心室内径(mm)^a	右心室内径(mm)^a	主动脉瓣环径(mm)
APVS组	26	61.7(35.0，120.0)	31.7(26.0，51.0)	8.7(4.7，13.4)	10.9(5.7，15.5)	9.2(3.2，15.6)	12.3(6.7，26.5)	5.1(2.1，6.8)
对照组	78	35.7(25.0，51.0)	28.6(25.0，33.0)	9.7(5.7，14.8)	11.0(6.8，18.0)	9.3(5.5，16.0)	9.9(6.2，17.0)	4.3(2.8，7.5)
Z值		－6.80	－3.22	－1.84	－0.19	－0.13	－3.10	－3.62
P值		<0.001	0.001	0.065	0.851	0.894	0.002	<0.001
组别	例数	肺动脉瓣环径(mm)	左肺动脉内径(mm)	右肺动脉内径(mm)	动脉导管内径(mm)^a	主动脉瓣流速(cm/s)	肺动脉瓣流速(cm/s)
APVS组	26	4.0(2.3，12.6)	6.8(2.4，22.0)	6.6(2.4，16.0)	2.7(2.0，3.5)	83.8(56.0，105.0)	157.4(63.0，248.0)
对照组	78	5.6(2.7，9.1)	2.3(1.3，3.9)	2.4(1.3，4.5)	2.5(1.3，4.9)	66.8(41.0，108.7)	60.1(40.0，95.4)
Z值		－5.17	－7.19	－7.25	－1.28	－4.64	－7.23
P值		<0.001	<0.001	<0.001	0.202	<0.001	<0.001

表5 识别胎儿APVS诊断的APVS组胎儿影响因素的多因素非条件logistics回归分析结果

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
胎龄	－0.619	0.308	4.052	0.044	0.538	0.295~0.984
右心室内径	1.020	0.509	4.020	0.045	2.772	1.024~7.511
心轴	0.286	0.097	8.748	0.003	1.331	1.101~1.608
心胸比	0.735	0.335	4.815	0.028	2.084	1.082~4.017

表5 识别胎儿APVS诊断的APVS组胎儿影响因素的多因素非条件logistics回归分析结果

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
胎龄	－0.619	0.308	4.052	0.044	0.538	0.295~0.984
右心室内径	1.020	0.509	4.020	0.045	2.772	1.024~7.511
心轴	0.286	0.097	8.748	0.003	1.331	1.101~1.608
心胸比	0.735	0.335	4.815	0.028	2.084	1.082~4.017

表6 2组胎儿左、右肺面积比较[cm², M(Q₁，Q₃)]

组别	例数	左肺面积	右肺面积
APVS组	18	2.4(1.3，4.3)	3.8(1.3，8.7)
对照组	54	3.3(1.1，6.1)	4.4(1.5，8.5)
Z值		－2.73	－1.58
P值		0.006	0.114

表6 2组胎儿左、右肺面积比较[cm², M(Q₁，Q₃)]

组别	例数	左肺面积	右肺面积
APVS组	18	2.4(1.3，4.3)	3.8(1.3，8.7)
对照组	54	3.3(1.1，6.1)	4.4(1.5，8.5)
Z值		－2.73	－1.58
P值		0.006	0.114

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