255:
normally developed and shows no structural malformations. Just like other autoimmune diseases, the autoimmune CHB shows signs of damage resulted from the autoantibodies attacking the normal tissue of the body, inflammation and fibrosis in the fetal heart tissue are the most common ones, mainly in the atrioventricular node. These antibodies lead to irreversible injuries in the atrioventricular node which heavily compromise the efficiency of the electrical conduction system, and this results in around 18% mortality rate and 70% of the live-born kids will need early
59:
35:
381:
Due to the rarity of this disease, there is a lack of comprehensive and high quality research about the different treatment options, and therefore, no specific treatment plan is followed globally. However, some studies have attempted to outline the most widely accepted approaches in dealing with CHB.
170:
In most cases, the congenital heart block is associated with other diseases, and therefore, the symptoms vary a lot between patients. However, low heart rate is usually the main clinical presentation that leads to the diagnosis. Also, the treatment varies as well due to the associated diseases and it
335:
There is a difference in diagnosis between low risk pregnancies where mothers do not have (or are not aware of) any autoimmune disease, and the high risk ones where mothers are known to have a specific autoimmune disease and / or are positive to anti Ro/La autoantibodies and / or had a CHB-affected
348:
between the weeks 18 - 30. The
Doppler is very important to assess the level of AV block as well as to check for other cardiac structural abnormalities that might be associated with CHB such as left atrial isomerism, valvular damages and big arteries inversion, while the echocardiogram is useful to
282:
Although the autoimmune CHB has a relatively high mortality and morbidity rates, the chance of kids from -mothers positive to anti-Ro\SSA and/or anti-La\SSB antibodies- to suffer from CHB is only around 1-5%, which suggests the existence of other factors to influence the disease such as genetic and
166:
The congenital heart block is a rare disease that affects around 1 child in every 15,000–20,000 births. However, its high mortality (which can be as high as 85% in some severe cases) makes the early diagnosis and intervention very important. CHB can be isolated, where the fetus does not suffer from
254:
In the autoimmune-mediated congenital heart block, autoantibodies are passively transferred through the placenta during gestation. The mother might be asymptomatic during or after pregnancy but she is usually positive to anti-Ro\SSA or anti-La\SSB antibodies. In this case, the fetus's heart is
323:
The cardiac structural diseases that are usually associated with the congenital heart block include the left atrial isomerism with or without atrioventricular septal defect. In addition, levo transpositions of the great arteries can accompany CHB but this is less common than the first one.
339:
In low risk pregnancies, testing the mothers' serum is not part of the routine prenatal tests. Therefore, the congenital heart block is usually diagnosed during a routine obstetrical ultra sound. The first symptom in most cases is a slow heart rate which can be detected using fetal
533:
Without considering the gender, the age of diagnosis or the associated diseases, mortality rate is around 20%. The majority of CHB-related deaths occur in the first 3 months after birth followed by fetal death, and it is less common to occur after the third month of age.
1564:
Jaeggi, Edgar T; Hamilton, Robert M; Silverman, Earl D; Zamora, Samuel A; Hornberger, Lisa K (2002-01-02). "Outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block: A single institution's experience of 30 years".
491:
In terms of the severity of the AV block, newborn kids with heart rate lower than 55 bpm have a negative outcome and higher chance to need pace-maker implantation, as well as kids with symptomatic bradycardia such as lower tolerance of exercises.
197:
and its right and left branches, leading to a lower heart rate. The atrioventricular block can be first degree or much more severe like a complete atrioventricular block (third degree). In addition, several changes in the ECG can be detected.
267:
This autoantibody is found in the serum of the majority of kids with autoimmune CHB, and therefore it is the one mostly linked with this disease. It attacks the proteins Ro52 and Ro60 in the antigen Ro\SSA in the fetal heart tissue.
445:
Plasma exchange in women positive to anti Ro/La autoantibodies has not been studied thoroughly, but it is suggested to have and effect on the titer of the antibodies in the mother's serum and therefore might have a preventive role.
319:
The presence of a cardiac structural abnormality is a major determination of the outcome of CHB. Its existence affects the conduction system of the heart and increases the mortality rate and the need for pace-maker implantation.
368:
Although the chance of having kids with CHB in anti Ro/La positive mothers is relatively low (1-5%), it is recommended that all mothers with autoimmune disease to be screened and seek consultation when decide to get pregnant.
1507:
Brucato, Antonio; Tincani, Angela; Fredi, Micaela; Breda, Silvia; Ramoni, Veronique; Morel, Nathalie; Costedoat-Chalumeau, Nathalie (2017-11-01). "Should we treat congenital heart block with fluorinated corticosteroids?".
372:
For mothers with at least one CHB-affected pregnancy, with 16 - 18% recurrence chance for the directly following pregnancy and an overall 9% chance in following ones, monitoring both the mother and the fetus is crucial.
217:) (EFE) is the obvious one and it occurs due to the damage caused by the maternal autoantibodies to the cardiac tissue of the fetus, and can lead to death in some cases. However, it is not a common feature of CHB.
291:
Several autoantibodies were suggested to have links with the autoimmune CHB, mainly the ones associated with the different autoimmune diseases that are common among women (such as the antibodies associated with
1448:
Ambrosi, Aurélie; Salomonsson, Stina; Eliasson, Håkan; Zeffer, Elisabeth; Skog, Amanda; Dzikaite, Vijole; Bergman, Gunnar; Fernlund, Eva; Tingström, Joanna; Theander, Elke; Rydberg, Annika (2012-03-01).
1663:
Chameides, L.; Truex, R. C.; Vetter, V.; Rashkind, W. J.; Galioto, F. M.; Noonan, J. A. (1977-12-01). "Association of maternal systemic lupus erythematosus with congenital complete heart block".
1608:
Mofors, Johannes; Eliasson, Håkan; Ambrosi, Aurelie; Salomonsson, Stina; Skog, Amanda; Fored, Michael; Ekbom, Anders; Bergman, Gunnar; Sonesson, Sven-Erik; Wahren-Herlenius, Marie (2019-05-01).
179:
The symptoms of the congenital heart block can vary due to the underlying problems that associate / lead to the CHB, and the features of CHB reflects the other manifestations of these diseases.
1396:
Buyon, Jill P.; Hiebert, Rudi; Copel, Joshua; Craft, Joseph; Friedman, Deborah; Katholi, Margaret; Lee, Lela A.; Provost, Thomas T.; Reichlin, Morris; Rider, Lisa; Rupel, Ann (1998-06-01).
546:
The survival rate is heavily affected by the associated diseases, and it is higher in autoimmune-mediated CHB patients compared to CHB patients with congenital cardiac structural problems.
495:
Isolated CHB has a better prognosis than the one associated with other disorders, the presence of congenital cardiac abnormalities increases the mortality rate. Also, kids presented with
410:
by decreasing the amount of anti Ro/La autoantibodies in the fetal serum. Therefore, they are used in the autoimmune-mediated CHB. Both the mother and the fetus might suffer from their
480:
Apart from these medications, a pace maker might be needed in around two thirds of the cases, and a procedure might be required when the heart has structural abnormalities.
488:
The outcome of the congenital heart block varies a lot due to several factors, such as the associated diseases, severity of the atrioventricular block, maternal age...etc.
171:
can be non-invasive (medications given to the pregnant woman or to the child), or a surgery in some cases when the CHB is resulted from anatomical disorders in the heart.
1755:
Fessel, W. Jeffrey (1974-12-01). "Systemic Lupus
Erythematosus in the Community: Incidence, Prevalence, Outcome, and First Symptoms; the High Prevalence in Black Women".
1107:
Wainwright, Benjamin; Bhan, Rohit; Trad, Catherine; Cohen, Rebecca; Saxena, Amit; Buyon, Jill; Izmirly, Peter (2019-10-08). "Autoimmune-mediated congenital heart block".
1320:
Brucato, A.; Frassi, M.; Franceschini, F.; Cimaz, R.; Faden, D.; Pisoni, M. P.; Muscarà, M.; Vignati, G.; Stramba-Badiale, M.; Catelli, L.; Lojacono, A. (August 2001).
1322:"Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women"
1171:
Friedman, Deborah M.; Rupel, Ann; Glickstein, Julie; Buyon, Jill P. (June 2002). "Congenital heart block in neonatal lupus: the pediatric cardiologist's perspective".
1838:
349:
detect other complications such as the hydrops fetalis. In the absence of cardiac structural diseases, the second step to confirm the diagnosis is to test the
280:, the links between this autoantibody and autoimmune CHB are less strong than the anti-Ro autoantibody and it usually accompanies it in the majority of cases.
1274:
Buyon, J. P.; Kim, M. Y.; Copel, J. A.; Friedman, D. M. (August 2001). "Anti-Ro/SSA antibodies and congenital heart block: necessary but not sufficient".
1398:"Autoimmune-Associated Congenital Heart Block: Demographics, Mortality, Morbidity and Recurrence Rates Obtained From a National Neonatal Lupus Registry"
1224:"Maternal and Fetal Factors Associated With Mortality and Morbidity in a Multi–Racial/Ethnic Registry of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus"
1451:"Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern"
137:
549:
Recurrence rate: mothers who had pregnancies associated with CHB, have a 16 - 18% chance of having kids with heart block in the following pregnancy.
311:
Also, some antigens of the fetal heart tissue (apart from the "Ro" and the "La") were studied, but no clear link with the autoimmune CHB was proven.
232:
In some cases the reason behind CHB remains unknown but in the great majority of affected kids, this disease is associated with the transference of
360:
In high risk pregnancies, the diagnosis is relatively easier as fetal and maternal screenings are part of the routine monitoring of the pregnancy.
220:
Another rare symptom that might accompany the autoimmune CHB is the disorder in the valvular function, and this happens due to the damage in the
477:
is relatively new approach, but it showed promising results in preventing the inflammation and other injuries result from it such as fibrosis.
236:
from the mother during gestation or with major cardiac structural abnormalities that lead to a disturbance in the conducting signals in the
1610:"Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero"
433:
are among the medications that have been used to treat CHB. They are used mainly to increase the heart rate in fetuses suffering from
1857:
1222:
Izmirly Peter M.; Saxena Amit; Kim Mimi Y.; Wang Dan; Sahl Sara K.; Llanos
Carolina; Friedman Deborah; Buyon Jill P. (2011-11-01).
240:. Also, in some rare cases, the congenital heart block was linked with viral infections or treatment with specific medications.
305:
1338:
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1839:
https://www.heart.org/en/health-topics/congenital-heart-defects/about-congenital-heart-defects/common-types-of-heart-defects
537:
Mortality rate is very high when the disease is diagnosed prenatally, and declines dramatically with older diagnosis ages.
831:
Michaëlsson, M.; Engle, M. A. (1972). "Congenital complete heart block: an international study of the natural history".
557:
327:
These developmental abnormalities can impair the conduction system of the heart by disrupting its anatomical structure.
293:
256:
17:
249:
459:
455:
214:
132:) or within the first 28 days after birth (neonatal period), some studies also include the diagnosis during early
1013:
Brito-Zerón, Pilar; Izmirly, Peter M.; Ramos-Casals, Manuel; Buyon, Jill P.; Khamashta, Munther A. (May 2015).
530:
More than 90% of the cases are associated with autoimmune disease and transference of maternal autoantibodies.
345:
556:
showed that the vast majority of the affected mothers are of a
Caucasian ethnicity, despite the fact that
149:
769:
Saxena, Amit; Izmirly, Peter M.; Mendez, Barbara; Buyon, Jill P.; Friedman, Deborah M. (November 2014).
415:
237:
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153:
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Around 60% - 70% of the patients will need pace-maker implantation regardless of the age of diagnosis.
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Among anti Ro/La positive women, older ones have higher possibility of having kids with heart block.
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in treating CHB, and the results of the different studies are contradictory. These steroids (such as
301:
297:
58:
98:
fluorinated steroids, beta agonists, IVIG, HCQ, pace maker implantation and maternal plasmapheresis.
1834:
1822:
277:
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showed some promising results in decreasing the possibility of having CHB's complications such as
167:
any other problems, or it can be a result of other diseases either in the child or in the mother.
1810:
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1204:
474:
437:. Although they showed positive results, some patients showed intolerance to their side effects.
67:
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Other manifestations of the congenital heart block can be related to the impact of the maternal
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within the heart muscle, which leads to the failure in pumping the blood efficiently into the
85:
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Kids with congenital heart block have higher chance to face health-related problems (such as
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341:
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145:
52:
496:
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of the mother for anti Ro/La autoantibodies using the enzyme-linked immunosorbent assay (
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933:
898:
803:
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is usually the first symptom of CHB to be detected in utero. Due to the block in the
1649:
1625:
1466:
1208:
1490:
899:"Congenital heart block: evidence for a pathogenic role of maternal autoantibodies"
771:"Prevention and treatment in utero of autoimmune-associated congenital heart block"
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1676:
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Table. I: The recurrence rate for pregnancies following the CHB-affected births
434:
426:
411:
182:
121:
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The congenital heart block occurs in 1 child in every 15,000 to 20,000 births.
430:
308:). However, the role of these autoantibodies was not studied comprehensively.
1776:
1723:
1684:
1633:
1586:
1529:
1474:
1423:
1347:
1295:
1192:
1128:
1038:
924:
844:
794:
718:
276:
This antibody attacks the ribonucleoprotein La48 on the surface of the fetal
1030:
516:
133:
1641:
1594:
1537:
1482:
1355:
1303:
1257:
1200:
1136:
1056:
942:
812:
736:
1784:
1741:
1431:
852:
1692:
399:
206:
398:) are used when the disease is diagnosed in utero as they can cross the
34:
1609:
1450:
1184:
391:
1339:
10.1002/1529-0131(200108)44:8<1832::AID-ART320>3.0.CO;2-C
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10.1002/1529-0131(200108)44:8<1723::AID-ART305>3.0.CO;2-0
148:. The result of CHB can be first, second, or third-degree (complete)
129:
915:
1109:
Best
Practice & Research Clinical Obstetrics & Gynaecology
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Some studies showed a genetic contribution to the autoimmune CHB.
354:
141:
125:
1794:
1835:
https://www.nhlbi.nih.gov/health-topics/congenital-heart-defects
1823:
https://my.clevelandclinic.org/health/diseases/17056-heart-block
1798:
1811:
https://rarediseases.org/rare-diseases/heart-block-congenital/
701:
Friedman, DM; Duncanson, LJ; Glickstein, J; Buyon, JP (2003).
1015:"The clinical spectrum of autoimmune congenital heart block"
543:
The disease seems to affect both males and females equally.
136:
to the definition of CHB. It refers to the disorder in the
512:
Mortality rate in CHB increases with earlier deliveries.
90:
fetal echocardiogram and
Doppler and ELISA for the mother
1706:
Kertesz, N. J.; Fenrich, A. L.; Friedman, R. A. (1997).
897:
Ambrosi, Aurélie; Wahren-Herlenius, Marie (2012-04-26).
42:
The conduction system of the heart (shown in yellow)
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402:without being deactivated. The main goal of using
1567:Journal of the American College of Cardiology
1402:Journal of the American College of Cardiology
156:) in which no electric signals move from the
8:
1708:"Congenital complete atrioventricular block"
224:as a result of the maternal autoantibodies.
390:There is no agreement on using fluorinated
315:Congenital cardiac structural abnormalities
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703:"A review of congenital heart block"
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1665:The New England Journal of Medicine
294:Systemic lupus erythematosus (SLE)
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1240:10.1161/CIRCULATIONAHA.111.033894
1614:Annals of the Rheumatic Diseases
1455:Annals of the Rheumatic Diseases
903:Arthritis Research & Therapy
205:in the autoimmune-mediated CHB.
1626:10.1136/annrheumdis-2018-214406
1467:10.1136/annrheumdis-2011-200207
707:Images in Paediatric Cardiology
306:Mixed connective tissue disease
346:Doppler ultra sound techniques
302:Progressive systemic sclerosis
1:
1757:Archives of Internal Medicine
1712:Texas Heart Institute Journal
1579:10.1016/S0735-1097(01)01697-7
1415:10.1016/S0735-1097(98)00161-2
1121:10.1016/j.bpobgyn.2019.09.001
1522:10.1016/j.autrev.2017.09.005
1173:Indian Journal of Pediatrics
1019:Nature Reviews. Rheumatology
787:10.1097/CRD.0000000000000026
558:Systemic Lupus Erythematosus
138:electrical conduction system
106:1 child in every 15000-20000
18:Neonatal lupus erythematosus
1677:10.1056/NEJM197712012972203
250:Autoimmune disease in women
244:Maternal autoimmune disease
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572:Percentage of Pregnancies
456:intravenous immunoglobulin
450:Intravenous immunoglobulin
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215:Endocardial fibroelastosis
15:
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1858:Congenital heart defects
1830:Congenital Heart Defects
1326:Arthritis and Rheumatism
1276:Arthritis and Rheumatism
272:Anti-La\SSB autoantibody
263:Anti-Ro\SSA autoantibody
1031:10.1038/nrrheum.2015.29
422:Beta-adrenergic agonist
283:environmental factors.
1806:Congenital Heart Block
833:Cardiovascular Clinics
499:and / or EFE and / or
336:pregnancy previously.
150:atrioventricular block
114:congenital heart block
28:Congenital heart block
416:adrenal insufficiency
238:atrioventricular node
187:atrioventricular node
154:atrioventricular node
124:that is diagnosed in
1510:Autoimmunity Reviews
775:Cardiology in Review
386:Fluorinated steroids
298:Rheumatoid arthritis
287:Other autoantibodies
565:
519:) than other kids.
503:have poor outcome.
406:is to mitigate the
1185:10.1007/bf02722656
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475:Hydroxychloroquine
470:Hydroxychloroquine
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1818:Heart Block Types
1671:(22): 1204–1207.
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1234:(18): 1927–1935.
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501:cardiomyopathy
485:
482:
471:
468:
464:cardiomyopathy
451:
448:
442:
441:Plasmapheresis
439:
423:
420:
387:
384:
378:
375:
365:
362:
342:echocardiogram
332:
329:
316:
313:
288:
285:
278:cardiomyocytes
273:
270:
264:
261:
259:implantation.
245:
242:
234:autoantibodies
229:
226:
203:autoantibodies
176:
173:
108:
107:
104:
100:
99:
96:
92:
91:
88:
82:
81:
78:
74:
73:
70:
64:
63:
50:
44:
43:
39:
38:
30:
29:
21:
13:
10:
9:
6:
4:
3:
2:
1870:
1859:
1856:
1855:
1853:
1840:
1836:
1832:
1828:
1824:
1820:
1816:
1812:
1808:
1804:
1797:
1786:
1782:
1778:
1774:
1770:
1766:
1762:
1758:
1751:
1748:
1743:
1739:
1734:
1729:
1725:
1721:
1717:
1713:
1709:
1702:
1699:
1694:
1690:
1686:
1682:
1678:
1674:
1670:
1666:
1659:
1656:
1651:
1647:
1643:
1639:
1635:
1631:
1627:
1623:
1619:
1615:
1611:
1604:
1601:
1596:
1592:
1588:
1584:
1580:
1576:
1572:
1568:
1560:
1558:
1556:
1554:
1552:
1550:
1548:
1544:
1539:
1535:
1531:
1527:
1523:
1519:
1515:
1511:
1503:
1501:
1497:
1492:
1488:
1484:
1480:
1476:
1472:
1468:
1464:
1460:
1456:
1452:
1444:
1442:
1438:
1433:
1429:
1425:
1421:
1416:
1411:
1407:
1403:
1399:
1392:
1390:
1388:
1386:
1384:
1382:
1380:
1378:
1376:
1374:
1372:
1370:
1368:
1366:
1362:
1357:
1353:
1349:
1345:
1340:
1335:
1331:
1327:
1323:
1316:
1314:
1310:
1305:
1301:
1297:
1293:
1289:
1285:
1281:
1277:
1270:
1268:
1264:
1259:
1255:
1250:
1245:
1241:
1237:
1233:
1229:
1225:
1218:
1215:
1210:
1206:
1202:
1198:
1194:
1190:
1186:
1182:
1178:
1174:
1167:
1165:
1163:
1161:
1159:
1157:
1155:
1153:
1151:
1149:
1147:
1143:
1138:
1134:
1130:
1126:
1122:
1118:
1114:
1110:
1103:
1101:
1099:
1097:
1095:
1093:
1091:
1089:
1087:
1085:
1083:
1081:
1079:
1077:
1075:
1073:
1071:
1069:
1067:
1063:
1058:
1054:
1049:
1044:
1040:
1036:
1032:
1028:
1024:
1020:
1016:
1009:
1007:
1005:
1003:
1001:
999:
997:
995:
993:
991:
989:
987:
985:
983:
981:
979:
977:
975:
973:
971:
969:
967:
965:
963:
961:
959:
957:
955:
953:
949:
944:
940:
935:
930:
926:
922:
917:
912:
908:
904:
900:
893:
891:
889:
887:
885:
883:
881:
879:
877:
875:
873:
871:
869:
867:
865:
863:
859:
854:
850:
846:
842:
839:(3): 85–101.
838:
834:
827:
825:
823:
819:
814:
810:
805:
800:
796:
792:
788:
784:
780:
776:
772:
765:
763:
761:
759:
757:
755:
753:
751:
749:
747:
743:
738:
734:
729:
724:
720:
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712:
708:
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697:
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645:
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635:
633:
631:
629:
627:
625:
623:
621:
617:
610:
603:
600:
599:
595:
593:Fetal Demise
592:
591:
587:
584:
583:
579:
576:
575:
571:
568:
567:
561:
559:
555:
554:United States
550:
547:
544:
541:
538:
535:
531:
528:
522:
520:
518:
513:
510:
507:
504:
502:
498:
493:
489:
483:
481:
478:
476:
469:
467:
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461:
457:
449:
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440:
438:
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432:
428:
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397:
396:dexamethasone
393:
385:
383:
376:
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370:
363:
361:
358:
356:
352:
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343:
337:
330:
328:
325:
321:
314:
312:
309:
307:
303:
299:
295:
286:
284:
279:
271:
269:
262:
260:
258:
251:
243:
241:
239:
235:
227:
225:
223:
218:
216:
212:
208:
204:
199:
196:
195:bundle of his
192:
188:
184:
180:
174:
172:
168:
164:
163:
159:
155:
151:
147:
143:
139:
135:
131:
127:
123:
119:
115:
105:
101:
97:
93:
89:
87:
83:
79:
75:
71:
69:
65:
60:
54:
51:
49:
45:
40:
36:
31:
26:
19:
1760:
1756:
1750:
1715:
1711:
1701:
1668:
1664:
1658:
1617:
1613:
1603:
1570:
1566:
1513:
1509:
1458:
1454:
1405:
1401:
1329:
1325:
1279:
1275:
1231:
1227:
1217:
1176:
1172:
1112:
1108:
1022:
1018:
906:
902:
836:
832:
778:
774:
713:(3): 36–48.
710:
706:
551:
548:
545:
542:
539:
536:
532:
529:
526:
523:Epidemiology
514:
511:
508:
505:
494:
490:
487:
479:
473:
453:
444:
425:
412:side effects
408:inflammation
389:
380:
371:
367:
359:
338:
334:
326:
322:
318:
310:
290:
275:
266:
253:
231:
219:
200:
181:
178:
175:Presentation
169:
165:
117:
113:
111:
1228:Circulation
435:bradycardia
427:Trebutaline
304:(PSS), and
183:Bradycardia
122:heart block
77:Usual onset
909:(2): 208.
611:References
517:infections
431:Sulbutamol
248:See also:
211:myocardium
162:ventricles
16:See also:
1777:0003-9926
1724:0730-2347
1685:0028-4793
1634:0003-4967
1587:0735-1097
1530:1568-9972
1475:0003-4967
1424:0735-1097
1348:0004-3591
1296:0004-3591
1193:0019-5456
1129:1521-6934
1115:: 41–51.
1039:1759-4804
925:1478-6362
845:0069-0384
795:1538-4683
719:1729-441X
377:Treatment
364:Screening
331:Diagnosis
257:pacemaker
134:childhood
120:) is the
103:Frequency
95:Treatment
80:in utero.
48:Specialty
1852:Category
1650:73476814
1642:30808622
1595:11755298
1538:28899797
1483:21953338
1356:11508435
1304:11508420
1258:21969015
1209:44783535
1201:12139139
1137:31685414
1057:25800217
943:22546326
813:25050975
737:22368629
577:Healthy
569:Outcome
484:Outcomes
400:placenta
392:steroids
207:Fibrosis
144:and the
130:in utero
68:Symptoms
1785:4433183
1742:9456483
1491:8446668
1432:9626848
1249:3206147
1048:5551504
934:3446439
853:4273004
804:4539276
728:3232542
209:of the
193:to the
160:to the
1783:
1775:
1740:
1733:325472
1730:
1722:
1693:917056
1691:
1683:
1648:
1640:
1632:
1593:
1585:
1536:
1528:
1489:
1481:
1473:
1430:
1422:
1354:
1346:
1302:
1294:
1256:
1246:
1207:
1199:
1191:
1135:
1127:
1055:
1045:
1037:
941:
931:
923:
851:
843:
811:
801:
793:
735:
725:
717:
454:Using
228:Causes
158:atrium
55:
1646:S2CID
1487:S2CID
1205:S2CID
355:ELISA
351:serum
142:aorta
126:fetus
1837:and
1781:PMID
1773:ISSN
1738:PMID
1720:ISSN
1689:PMID
1681:ISSN
1638:PMID
1630:ISSN
1591:PMID
1583:ISSN
1534:PMID
1526:ISSN
1479:PMID
1471:ISSN
1428:PMID
1420:ISSN
1352:PMID
1344:ISSN
1300:PMID
1292:ISSN
1254:PMID
1197:PMID
1189:ISSN
1133:PMID
1125:ISSN
1053:PMID
1035:ISSN
939:PMID
921:ISSN
849:PMID
841:ISSN
809:PMID
791:ISSN
733:PMID
715:ISSN
588:16%
585:CHB
580:73%
462:and
429:and
344:and
112:The
1765:doi
1761:134
1728:PMC
1673:doi
1669:297
1622:doi
1575:doi
1518:doi
1463:doi
1410:doi
1334:doi
1284:doi
1244:PMC
1236:doi
1232:124
1181:doi
1117:doi
1043:PMC
1027:doi
929:PMC
911:doi
799:PMC
783:doi
723:PMC
604:2%
596:2%
460:EFE
357:).
118:CHB
1854::
1779:.
1771:.
1759:.
1736:.
1726:.
1716:24
1714:.
1710:.
1687:.
1679:.
1667:.
1644:.
1636:.
1628:.
1618:78
1616:.
1612:.
1589:.
1581:.
1571:39
1569:.
1546:^
1532:.
1524:.
1514:16
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1499:^
1485:.
1477:.
1469:.
1459:71
1457:.
1453:.
1440:^
1426:.
1418:.
1406:31
1404:.
1400:.
1364:^
1350:.
1342:.
1330:44
1328:.
1324:.
1312:^
1298:.
1290:.
1280:44
1278:.
1266:^
1252:.
1242:.
1230:.
1226:.
1203:.
1195:.
1187:.
1177:69
1175:.
1145:^
1131:.
1123:.
1113:64
1111:.
1065:^
1051:.
1041:.
1033:.
1023:11
1021:.
1017:.
951:^
937:.
927:.
919:.
907:14
905:.
901:.
861:^
847:.
835:.
821:^
807:.
797:.
789:.
779:22
777:.
773:.
745:^
731:.
721:.
709:.
705:.
619:^
466:.
418:.
300:,
296:,
1787:.
1767::
1744:.
1695:.
1675::
1652:.
1624::
1597:.
1577::
1540:.
1520::
1493:.
1465::
1434:.
1412::
1358:.
1336::
1306:.
1286::
1260:.
1238::
1211:.
1183::
1139:.
1119::
1059:.
1029::
945:.
913::
855:.
837:4
815:.
785::
739:.
711:5
213:(
128:(
116:(
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