Table 1.
Literature summery about the initial diagnosis of fetal first-degree autoimmune-associated congenital heart block.
| References | Cases n. | Diagnosed methods | GWs | Mother's disease | Mother's positive autoantibody (titer) | Fetal AV intervals (ms) [z-scores] | Time of first therapy after diagnosis | Therapy medicines (dose) | Treated duration | Potential adverse effects of steroids | Prenatal results before birth | Postnatal therapy | Follow-up time | Follow-up results |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Vesel et al. (36) | Case 1 | PD | 25 | SS | Anti-SSA/Ro | 185 | 0 | Dex. (4 mg/day) | To 29 w | Severe oligohydra-mnio | 1 | Ventricular endocardial pacemaker | 4 m | 1 |
| Friedman et al. (34, 37) | Case 2 | PD MV-Ao | 20 | SLE/UAS/asym.? | anti-SSA/Ro (Mean 16128) | 165 | 0 | Dex. (4 mg/ day) | Until delivery | – | 1 | – | 1 y | 1 |
| Case 3 | PD MV-Ao | 22 | SLE/UAS/asym.? | Anti-SSA/Ro (Mean 16128) | 160 | 0 | Dex. (4 mg/day) | To 26w | Oligohydra-mnio | 2 | – | 1 y | 1 | |
| Rein et al. (38) | Case 4 | FKCG | 21 | SLE | anti-SSA/Ro anti-SSB/La | 149 [≥2] | 0 | Dex. (4 mg/day) | Until delivery | – | 1 | Pre. (0.1 mg/kg for 6 w) | 1–6 y | 1 |
| Case 5 | FKCG | 25 | SS | Anti-SSA/Ro Anti-SSB/La | 126 [≥2] | 0 | Dex. (4 mg/day) | Until delivery | – | 1 | Pre. (0.1 mg/kg for 6 w) | 1–6 y | 1 | |
| Case 6 | FKCG | 26 | SLE | Anti-SSA/Ro Anti-SSB/La | 110 [≥2] | 0 | Dex. (4 mg/day) | Until delivery | – | 1 | Pre. (0.1 mg/kg for 6 w) | 1–6 y | 1 | |
| Case 7 | FKCG | 34 | SLE | Anti-SSA/Ro Anti-SSB/La | 134 [≥2] | 0 | Bet.+Dex. (4 mg/day) | Until delivery | – | 1 | Pre. (0.1 mg/kg for 6 w) | 1–6 y | 1 | |
| Case 8-A | FKCG | 32 | MCTD | Anti-SSA/Ro Anti-SSB/La | 115 [≥2] | 0 | Dex. (4 mg/day) | Until delivery | – | 1 | Pre. (0.1 mg/kg for 6 w) | 1–6 y | 1 | |
| Case 8-B | 33 | 115 [≥2] | – | 1 | Pre. (0.1 mg/kg for 6 w) | 1–6 y | 1 | |||||||
| Jaeggi et al. (39) | Case 9 | Fetal echo | 23 | – | Anti-SSA/Ro (>100 U/ml) | 250 [+14] | 0 | Steroids +IVIG | – | – | 2 | – | – | 5 |
| Izmirly et al. (40) | Case 10-11 | – | – | SLE | Anti-SSA/Ro Anti-SSB/La | – | – | Dex. | – | – | 1 | – | – | 1 |
| Tunks et al. (41) | Case 12 | PD MV-Ao | 22 | SLE | Anti-SSA/Ro (mean 443) Anti-SSB/La (mean 334.7) Anti-Smith (mean 40.3) Anti-RNP (mean 57) | – | 0 | Dex. (4 mg/day) | – | – | 3 (2 days later) | – | – | 3 |
| Case 13 | PD MV-Ao | – | – | 150–160? | 0 | Dex. | Until delivery | – | 1 | – | – | 1 | ||
| Case 14 | – | – | 150–160? | 0 | Dex. | Until delivery | – | 1 | – | – | 1 | |||
| Case 15 | – | – | 150–160? | 0 | Dex. | Until delivery | – | 2 | – | – | 2 | |||
| Case 16 | 19+ | SS, Hypothy-roidism | – | 0 | Steroids+ IVIG+dex. | Until delivery | – | 2 | – | – | 2 | |||
| Cuneo et al. (42) | Case 17 | PD MV-Ao | 19+ | – | Anti-SSA/Ro | – | 0 | Dex. | - | – | 1 | – | – | 1 |
| Sonesson et al. (35) | Case 18 | PD MV-Ao +SVC-Ao | 23 | SS | Anti-Ro52 | 165 [6.3] | 0 | Bet. (4 mg/day) | Until delivery | – | 2 | – | 1 y | 2 |
| Case 19 | 24 | SS | 16 4 [6.0] | 0 | Bet. (4 mg/day) | Until delivery | – | 2 | – | 4 y | 2 | |||
| Sonesson et al. (43) | Case 20 | PD MV-Ao +SVC-Ao | 18–24? | – | Anti-SSA/Ro Anti-SSB/La | – | 0 | No therapy | Until delivery | – | 3 (in 6 days when beta. started) | – | – | 3 |
| Case 21–2 | PD MV-Ao +SVC-Ao | 18–24? | – | Anti-SSA/Ro Anti-SSB/La | – | – | No therapy | – | – | 2 | – | Few weeks | 1 | |
| Case 24–26 | – | – | No therapy | – | – | 1 | – | 1 | ||||||
| Friedman et al. (37) | Case 27 | PD MV-Ao | 32 | SLE/UAS/asym.? | Anti-SSA/Ro (Mean 16128) | 170 | – | No therapy | – | – | 1 | – | 3 y | 2 |
| Skog et al. (44) | Case 28–30 | Fetal echo | 18–24? | SLE/SS/other? | Anti-Ro52 | – | – | No therapy | – | – | 2 | – | 1 m | 1 |
| Case 31–35 | – | – | No therapy | – | – | 1 | – | 1 | ||||||
| Jaeggi et al. (39) | Case 36 | Fetal echo | 22 | - | Anti-SSA/Ro (55 U/ml) | – | – | No therapy | – | – | 5 | – | – | 5 |
| Izmirly et al. (40) | Case 37 | – | – | SLE | Anti-SSA/Ro Anti-SSB/La | – | – | No therapy | – | – | 2 | – | 3 y | 2 |
| Krishnan et al. (45) | Cases 38-41 | PD MV-Ao | 16–28? | – | Anti-SSA/Ro | >140? | – | No therapy | – | – | 1 | – | – | 5 |
| Case 42 | 2 | - | – | 5 | ||||||||||
| Case 43 | 16–28? | – | 160–170? | – | No therapy | – | – | 2 | – | – | 5 | |||
| Doti et al. (46) | Case 44 | Fetal echo | 25+ | – | Anti-SSA/Ro Anti-SSB/La | – | – | No therapy | – | – | 2 | – | – | 2 |
| Cuneo et al. (42) | Case 45 | PD MV-Ao | 26+ | – | Anti-SSA/Ro | – | – | No therapy | – | – | 1 | – | – | 1 |
| Case 46 | 25+ | – | – | – | No therapy | – | – | 1 | – | – | 1 | |||
| Case 47 | 21+ | – | – | – | No therapy | – | – | 1 | – | – | 1 |
GWs, gestational weeks; AVB, atrioventricular block; PD: pulsed-wave Doppler echocardiography; MV-Ao, from the intersection of the mitral E- and A-waves to the onset of the ventricular ejection wave in the aortic outflow; SVC-Ao, from the beginning of the retrograde venous a-wave in the SVC to the beginning of the aortic ejection wave; TDI, tissue Doppler imaging, echo: echocardiography; Aa-Sa, between atrial contraction and ventricular systole; FKCG, fetal kinetocariogram, SLE, systemic lupus erythematosus; UAS, undifferentisted autoimmune syndrome; asym., asymptomatic; SS, Sjögren syndrome; CTD, connective tissue disease; MCTD, mixed CTD; Dex., dexamethasone; Bet., betamethasone; Pre., prednisone; echo, echocardiogram; HCQ, hydroxychloroquine; IVIG, intravenous immune globulin; FGR, fetal growth restriction; LBW, low birth weight.
?: the specific value was not determine and only the range was provided in original study.
The bold type of word: highlighting the cases about the progression of the first-degree AVB to third-degree AVB.
Time from initiation to therapy: 0 mean that the therapy for fetal first-degree AVB was started immediately after the diagnosis was made.
Prenatal results: 1: conversation to sinus rhythm; 2: not progressed and sustained first-degree AVB; 3: progressed to third-degree AVB (complete AVB); 4: died; 5: alive but the detail conditions cannot be obtained from original study.
Follow-up results: 1: healthy and normal development; 2: sustained first-degree AVB; 3: progressed to high-degree AVB; 4: died; 5: alive but the detail conditions cannot be obtained from original study probably attributed to loss of follow-up.