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中华妇幼临床医学杂志(电子版) ›› 2023, Vol. 19 ›› Issue (04) : 410 -418. doi: 10.3877/cma.j.issn.1673-5250.2023.04.006

论著

胎儿先天性肺动脉瓣缺如综合征的超声特征及预后分析
薛超, 张烨, 赵映, 韩建成, 谷孝艳, 孙琳, 刘晓伟, 宋伟, 何怡华†()   
  1. 北京市心肺血管疾病研究所-首都医科大学附属北京安贞医院心脏超声医学中心，北京安贞医院胎儿心脏病母胎医学中心，北京　100029
    首都医科大学附属北京妇产医院/北京妇幼保健院围产医学部，北京　100026
  • 收稿日期:2023-02-04 修回日期:2023-07-02 出版日期:2023-08-01
  • 通信作者: 何怡华

Ultrasonographic characteristics and prognosis of fetal congenital absent pulmonary valve syndrome

Chao Xue, Ye Zhang, Ying Zhao, Jiancheng Han, Xiaoyan Gu, Lin Sun, Xiaowei Liu, Wei Song, Yihua He†()   

  1. Echocardiography Medical Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029
    Maternal-Fetal Medicine Center of Fetal Heart Disease, Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
  • Received:2023-02-04 Revised:2023-07-02 Published:2023-08-01
  • Corresponding author: Yihua He
  • Supported by:
    National Natural Science Foundation of China(U21A20523); National Natural Science Foundation of China(82170301); Project of Beijing Lab for Cardiovascular Precision Medicine(PXM2018_014226_000013); Project of Beijing Key Laboratory of Maternal-Fetal Medicine in Fetal Heart Disease(BZ0308)
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引用本文：

薛超, 张烨, 赵映, 韩建成, 谷孝艳, 孙琳, 刘晓伟, 宋伟, 何怡华. 胎儿先天性肺动脉瓣缺如综合征的超声特征及预后分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 410-418.

Chao Xue, Ye Zhang, Ying Zhao, Jiancheng Han, Xiaoyan Gu, Lin Sun, Xiaowei Liu, Wei Song, Yihua He. Ultrasonographic characteristics and prognosis of fetal congenital absent pulmonary valve syndrome[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 410-418.

目的

探讨胎儿肺动脉瓣缺如综合征(APVS)的超声特征、合并畸形特点及预后。

方法

选择2010年11月至2020年12月于北京安贞医院母胎医学中心诊断为APVS的26例胎儿(胎儿1~26)为研究对象，纳入APVS组；选取同期于同一家医院产科建卡，并定期产前检查的78例与APVS组胎儿胎龄匹配的健康胎儿作为对照，纳入对照组。收集2组胎儿诊断时胎龄、心胸比、心轴与是否合并心内、外畸形及心力衰竭，室间隔缺损(VSD)大小，主动脉骑跨率，肺面积，主动脉瓣环径，肺动脉瓣环径、肺动脉主干及分支直径，左心房、左心室、右心房、右心室内径，主动脉瓣流速及肺动脉瓣流速，以及4例胎儿的拷贝数变异测序(CNV-seq)结果。采用多因素非条件logistics回归分析，对识别胎儿APVS诊断的影响因素进行分析。本研究遵循的程序符合北京安贞医院伦理委员会制定的标准，并获得该伦理委员会批准(批准文号：2023135X)。所有胎儿孕母均签署知情同意书，终止妊娠者签署胎儿大体解剖及遗传学检测同意书。

结果

①本研究APVS组26例胎儿中，法洛四联症(TOF)型APVS胎儿为17例(17/26，65.4%)，孤立型为4例(4/26，15.4%)，合并复杂心脏畸形胎儿为5例(5/26，19.2%)。②本研究APVS组26例胎儿超声心动图表现为肺动脉瓣环狭窄，肺动脉瓣叶缺如或发育不良，肺动脉主干及左右分支瘤样扩张。彩色多普勒血流显像(CDFI)结果显示，这26例胎儿肺动脉瓣重度反流，脉冲频谱多普勒(PW)测量结果显示，其中23例胎儿肺动脉血流速度为增快。③本研究APVS组26例胎儿中，胎死腹中为1例，引产终止妊娠为18例，7例失访，妊娠结局不详。这19例不良妊娠结局胎儿中，12例经尸检，其肺动脉瓣缺如等心脏结构畸形被证实，其中1例胎儿超声心动图将肺动脉瓣缺如综合征，误诊为肺动脉瓣狭窄。④2组胎儿心轴、心胸比、右心室内径、主动脉瓣环径、肺动脉瓣环径、左肺动脉内径、右肺动脉内径、主动脉瓣流速、肺动脉瓣流速比较，差异均有统计学意义(P<0.05)。⑤对APVS胎儿相关临床资料的多因素非条件logistics回归分析结果显示，胎龄(OR＝0.538，95%CI：0.295~0.984，P＝0.044)，右心室内径(OR＝2.772，95%CI：1.024~7.511，P＝0.045)，心轴(OR＝1.331，95%CI：1.101~1.608，P＝0.003)及心胸比(OR＝2.084，95%CI：1.082~4.017，P＝0.028)为识别胎儿APVS的影响因素。

结论

肺动脉瓣叶缺如，或者发育不良瓣叶残瘠，肺动脉瓣环狭窄、肺动脉主干或分支瘤样扩张为APVS胎儿的典型超声特征，结合胎儿心轴、右心室内径、心胸比，可提高临床对APVS胎儿的产前超声诊断率。APVS可影响胎儿左侧肺发育，产前超声明确诊断胎儿APVS，可为产前咨询及生后治疗方案的制定提供重要依据。

关键词: 肺动脉瓣缺如综合征, 超声心动图, 产前诊断, Logistic模型, 胎儿
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
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
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