General information. Of the 400 cases, the mean age of the pregnant women was 31.68 ± 4.20 years (range, 20–46), and the median gestational age at ultrasound diagnosis was 22.9 ± 4.75 weeks (range, 11–40). 359(89.75%, 359/400) of all the cases were singletons, and 41(10.25%, 41/400) were twins. Among the 400 cases, 178 (44.5%, 178/400) cases had concomitant extracardiac abnormalities. The genetic examination was performed in 204 (51.00%, 204/400) cases, among which, 44 (21.57%, 44/204) were detected with pathogenic genetic abnormalities. Overall, there were 275(68.75%, 275/400) fetuses underwent TOP and 2(0.50%, 2/400) fetal death (FD).
Categorization of fetal cardiac defects and pregnancy outcome. Prenatal ultrasound showed 237 cases of single heart defects (59.25%, 237/400), including 122 cases with no extracardiac defects in Group A (30.50%, 122/400), while 115 with extracardiac abnormalities belonged to group B (28.75%, 115/400).163 cases were complex multiple cardiac defects (40.75%,163/400), of which 100 without extracardiac abnormalities belonged to group C(25.00%, 100/400), and 63 with extracardiac abnormalities belonged to group D (15.75%, 63/400).
Under group A, 44.26% (54/122) were terminated, which was lower than the other three groups. And 86.09% (99/ 115) were terminated, 0.87% (1/115) were FDs in group B. In group C, there was 70% (70/100) underwent TOP and 1% (1/100) FD, and in group D, the termination rate was 82.54% (52/63) (Table 2).
Table 2
Category of fetal cardiac defects and detection rates of pathogenic genetic abnormalities and pregnancy outcomes in each group.
Group | N (%) | Genetic detection | Pathological genetic anomalies(n) | Detection rate (%) | Live births (%) | TOP (%) | FD (%) |
A | 122(30.50%) | 53 | 8 | 15.09% | 68(55.74%) | 54(44.26%) | |
B | 115(28.75%) | 61 | 24 | 39.34% | 15(13.04%) | 99(86.09%) | 1(0.87%) |
C | 100(25.00%) | 49 | 3 | 6.12% | 29(29.00%) | 70(70.00%) | 1(1.00%) |
D | 63(15.75%) | 41 | 9 | 21.95% | 11(17.46%) | 52(82.54%) | |
Total | 400(100%) | 204 | 44 | 21.57% | 123(30.75%) | 275(68.75%) | 2(0.50%) |
Ultrasound results of fetal cardiac defects. Overall, ventricular septal defect was the most common cardiac abnormality and was present in 96 cases (24.00%), followed by tetralogy of Fallot in 52 cases (13.00%), coarctation of the aorta in 34 cases (8.5%), atrioventricular septal defect in 26 cases (6.5%), and single atrium and single ventricle in 22 cases (5.5%). The detailed data are presented in Table 3.
Table 3
The spectrum of fetal cardiac defects
Cardiac lesions | N | % |
Ventricular septal defect | 96 | 24.00% |
Tetralogy of Fallot | 52 | 13.00% |
Coarctation of aorta | 34 | 8.50% |
Atrioventricular septal defect | 26 | 6.50% |
Single atrium + single ventricle | 22 | 5.50% |
Double outlet right ventricle | 21 | 5.25% |
Persistent left superior vena cava | 19 | 4.75% |
Right aortic arch | 16 | 4.00% |
Complete transposition of great arteries | 15 | 3.75% |
Pulmonary valve stenosis | 15 | 3.75% |
Cardiac malposition | 12 | 3.00% |
Truncus arteriosus | 12 | 3.00% |
Interruption of aortic arch | 9 | 2.25% |
Mitral and Tricuspid valve cleft | 9 | 2.25% |
Pulmonary atresia | 8 | 2.00% |
Cardiac arrhythmias | 6 | 1.50% |
Anomalous pulmonary venous return | 5 | 1.25% |
Hypoplastic left heart syndrome | 5 | 1.25% |
Aberrant right subclavian artery | 4 | 1.00% |
Atria septal defect | 4 | 1.00% |
Other CHD | 4 | 1.00% |
Cardiac tumors | 3 | 0.75% |
Noncompaction of the Ventricular Myocardium, NVM | 3 | 0.75% |
Total | 400 | 100.00% |
Prognosis grading. According to the major cardiac defects, the fetuses were divided into different stratification categories based on the expected prognosis and grades. 39 cases (9.75%) were classified under Grade Ⅰ, 163 (40.75%) under Grade Ⅱ, 151 (37.75%) in Grade Ⅲ, and 45 (11.25%) in Grades Ⅳ. 2 cases cannot be stratified, include one case had massive tricuspid regurgitation with portosystemic fistula, and one case of foramen ovale premature closure. The termination rate in Grade Ⅰ was 35.89% (14/39), in Grade Ⅱ was 51.53% (84/163), in Grade Ⅲ was 88.74% (134/151), and in Grade Ⅳ was 95.56% (43/45) (Table 4).
Table 4
Prognostic classification of fetal cardiac defects and termination rate in each grade
Grade | n | % | TOP(n) | Termination rate |
Ⅰ | 39 | 9.75% | 14 | 35.89% |
Ⅱ | 163 | 40.75% | 84 | 51.53% |
Ⅲ | 151 | 37.75% | 134 | 88.74% |
Ⅳ | 45 | 11.25% | 43 | 95.56% |
| 2 | 0.50% | 0 | 0 |
Total | 400 | 100.00% | 275 | 68.75% |
Inheritance analysis of fetuses with cardiac defects. Among 204 cases that have obtained inheritance analysis, 44 cases (21.57%, 44/204) were identified with pathogenic genetic abnormalities, of which 40 cases (19.61%, 40/204) were detected with chromosomal abnormalities, and 37 of these cases were identified with numerical chromosomal abnormalities, including 15(7.35%) cases of 21-trisomy, 11(5.39%)cases of 18-trisomy, 3(1.47%) cases of 13-trisomy, one case with Turner syndrome, and partial aneuploidy including 1case with 18-trisomy and monosomy X, 1case with 18-trisomy and XYY,1case with18-trisomy and X trisomy, and mosaic including 1case with mosaic trisomy 18, 1case of mosaic monosomy 18, and 1case of mosaic monosomy X, and 1case of mosaic trisomy 7. The rest 3 cases were chromosome structural abnormality, involving one case each of deletion of 10q25q21q12, deletion of 13q22q32, and deletion of 6q21q25. Besides, there were three cases of pathogenic microdeletion/microduplication, including Xq28 microduplication, 5q (35.2–35.3) microdeletion, and 21p+. In addition, there was one case of TSC2 gene mutation (Table 5).
Table 5
Results of pathogenic genetic abnormalities.
Etiology | type | n | % |
Aneuploidy(n = 37) | Trisomy 21 | 15 | 7.35% |
Trisomy 18 | 11 | 5.39% |
Trisomy 13 | 3 | 1.47% |
45x | 1 | 0.49% |
Trisomy 18 and monosomy X | 1 | 0.49% |
Trisomy 18 and XYY | 1 | 0.49% |
Trisomy 18 and trisomy X | 1 | 0.49% |
mosaic monosomy 18 | 1 | 0.49% |
mosaic trisomy 18 | 1 | 0.49% |
mosaic monosomy X | 1 | 0.49% |
mosaic trisomy 7 | 1 | 0.49% |
Abnormality of chromosome structure(n = 3) | 46, XN, ?ins(10)(q25q21q12)dn | 1 | 0.49% |
46, XN, del(13)(q22q32) | 1 | 0.49% |
46, XN, del(6)(q21q25) | 1 | 0.49% |
Chromosomal anomalies | | 40 | 19.61% |
microdeletion/microduplication(n = 3) | ChrXq28 0.873 Mb dup | 1 | 0.49% |
Chr5q35.2-35.3 1.548 Mb del | 1 | 0.49% |
46 XN, 21p + denovo | 1 | 0.49% |
Gene mutation(n = 1) | TSC2: C.2113G > A | 1 | 0.49% |
Total | | 44 | 21.57% |
The detection rate of pathogenic genetic abnormalities in group B (39.34%) and D (21.95%) was significantly higher than that in group A (15.09%) and C (6.12%). Overall, the detection rate of pathogenic genetic abnormalities in patients with extracardiac anomalies was significantly higher than that in those without extracardiac anomalies (χ2 = 14.025, p < 0.001) (Table 2 and Table 6).
Table 6
The relation of pathogenic genetic abnormalities with extracardiac anomalies.
| pathogenic genetic abnormalities | χ2 | P |
Yes | No |
Associated extracardiac anomalies | YES | 33 | 69 | 14.025 | 0.000 |
NO | 11 | 91 |
Risk factor analysis of the fetuses with cardiac defects on termination of pregnancy. We analyzed the factors that might influence the decision to terminate of pregnancy. Unconditional logistic regression analysis suggested that diagnosed gestational age, combined with other cardiac defects, co-existence of extracardiac defects, harbored with pathogenic genetic anomalies, and prognosis grades were strongly associated with the parental decision to terminate pregnancy.
Fetuses diagnosed at a later gestational age were less likely to terminate pregnancy (95% CI: 0.772, 0.869). Fetuses presented with extracardiac abnormalities were at 4.420 times higher risk of pregnancy termination compared to those without (95% CI: 2.714,7.199). Fetuses with multiple and complex cardiac defects were at 1.634 times higher risk of pregnancy termination compared to single cardiac defects (95% CI: 1.049, 2.544). Besides, fetuses that harbored pathogenic genetic abnormalities were a 5.094 times higher likelihood of termination (95% CI: 1.732, 14.983). In addition, the prognosis grades also significantly affect the likelihood of termination (95% CI:2.992, 6.173) (Table 7), and the risk was 4.297 times higher when the grades increase one level.
When considering other factors that might influence the decision on termination of pregnancy, we included age, gravidity, and parity, and multiple logistics regression analysis revealed that co-existence of extracardiac defects (OR 7.347, CI: 3.674, 14.694), with pathogenic genetic anomalies (OR 7.493, CI: 2.051, 27.372), higher prognosis grades (OR 6.307, CI: 3.943, 10.088) and diagnosed in later gestational age (OR 0.819, CI:0.753, 0.890) were remained significantly associated with the termination of fetal cardiac defects, while presence of other cardiac defects (p = 0.624) was not statistically significant (Table 7).
Table 7
Impacting factors on the decision of termination of pregnancy
| | TOP | χ2 | Univariate analysis | Multivariable analysis | |
No | Yes (%) | P | OR (95%CI) | P | OR (95%CI) | |
Extracardiac anomalies | No | 98 | 124 (55.86%) | 38.606 | 0.000 | 4.420(2.714,7.199) | 0.000 | 7.347(3.674,14.694) |
Yes | 27 | 151(84.83%) |
Complex multiple cardiac defects | No | 84 | 153(64.56%) | 4.759 | 0.030 | 1.634(1.049,2.544) | 0.624 | 1.167(0.629,2.164) |
Yes | 41 | 122(74.85%) |
Pathogenic genetic abnormalities | No | 54 | 106(66.25%) | 11.307 | 0.003 | 5.094(1.732,14.983) | 0.002 | 7.493(2.051,27.372) |
Yes | 4 | 40(90.91%) |
unknown | 67 | 129(65.82%) |
Prognosis grades | | | | | 0.000 | 4.297(2.992,6.173) | 0.000 | 6.307(3.943,10.088) |
Diagnosed gestational age | | | | | 0.000 | 0.819(0.772,0.869) | 0.000 | 0.819(0.753,0.890) |
MDT prenatal counseling and management. A total of 29 (7.25%, 29/400) fetuses with cardiac lesions received prenatal multidisciplinary counseling, including 12 fetuses (41.38%) in group A and one fetus (3.45%) in group B, 11 (37.93%) cases in group C, and 5(56.4%) cases in group D (Table 8). During the follow-up, 8 fetuses were terminated and 21 were born, of which 4 infants received surgical treatment after birth and recovered well. The rest 17 infants continued to be followed up.
Compared to the cases without MDT caring, the MDT group had a significantly lower rate of pregnancy termination particularly in groups C and D (36.36%vs. 74.26% in group C; 20.00% vs. 87.93% in group D, p < 0.001) (Table 9 and Fig. 1).
Table 8
Category of groups in MDT caring fetuses.
| N = 29 | % |
A | 12 | 41.38% |
B | 1 | 3.45% |
C | 11 | 37.93% |
D | 5 | 17.24% |
Total | 29 | 100.00% |
Table 9
Comparison of prognosis between fetuses with and without MDT caring in each group
Group | MDT | N | TOP(n) | Termination rate | P |
A | Yes | 12 | 3 | 25.00% | 0.157 |
No | 110 | 51 | 46.36% |
B | Yes | 1 | 0 | 0 | 0.139 |
No | 114 | 99 | 86.84% |
C | Yes | 11 | 4 | 36.36% | 0.026 |
No | 89 | 66 | 74.26% |
D | Yes | 5 | 1 | 20.00% | 0.003 |
No | 58 | 51 | 87.93% |