en POLSKI
eISSN: 2449-6731
ISSN: 2449-6723
Prenatal Cardiology
Current issue Archive About the journal Editorial board Abstracting and indexing Contact Instructions for authors Ethical standards and procedures
 
1/2022
 
Share:
Share:
more
 
 
Review paper

Congenital heart block in fetuses of anti-SSA/SSB-positive mothers – treatment options, review 2021

Monika Opacian-Bojanowska
1
,
Julia Murlewska
2
,
Paulina Kordjalik
2
,
Iwona Strzelecka
3

1.
Paediatric Cardiosurgery, Copernicus PL, Gdansk, Poland
2.
Department of Prenatal Cardiology, Polish Mother’s Memorial Hospital Research Centre, Lodz, Poland
3.
Department of Fetal Malformation Diagnosis and Prevention, Medical University of Lodz, Public Health Faculty, Poland
Prenat Cardio 2022
Online publish date: 2022/09/06
Article file
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
 

Introduction

Among all cases of congenital heart block, third degree block occurs in 80% of cases; the other 20% are first and second degree blocks equally. In 50-55% of fetuses complete heart block (CHB) accompanies congenital heart defects (mainly left isomerism, corrected transposition of great arteries) because of structural abnormalities of the conductive system; not much can be done treatment wise because this kind of block will not respond to anti-inflammatory therapy.
Immune-mediated CHB with normal heart anatomy accounts for another 40% of cases, and in 5-10% the underlying cause remains unknown. In this paper we will focus only on autoimmune complete heart block, which is observed in approximately 2% of fetuses of anti-SSA/SSB-positive mothers. Up to one-third of women suffering from lupus erythematosus (LE), Sjogren’s syndrome, undifferentiated connective tissue disease, previously asymptomatic, are diagnosed with fetal cardiac problems, which subsequently leads to diagnosis of maternal subclinical disease. The prevalence of 1 in 15-20,000 live births makes it a rare condition, small group of patients is the reason for mainly retrospective studies and difficulties in establishment of therapy consensus. The recurrence rate for anti-SSA/SSB-positive mothers who previously had a CHB-affected child is as high as 19%. Pregnant women with high titres of SSA autoantibodies are considered at high risk [1]. CHB in pregnancies with low titres of anti-SSA or anti-SSB antibodies appear rarely.
A consequence of atrioventricular dissociation and the main diagnostic symptom is bradycardia, typically 50-70 bpm of ventricular escape rhythm, which presents most often around 16-29 weeks of gestation; however, autoantibodies can cross the placenta as early as at 11 weeks [2]. Inflammation and fibrosis of the atrioventricular (AV) node cause atrioventricular block (AVB) of various degrees; thus, thir degree block is considered to be irreversible. The mortality rate reaches 19% (70% of deaths refer to the prenatal period) [3, 4]. Additional factors for bad prognosis are as follows: early diagnosis (< 20 weeks), hydrops fetalis, ventricular escape rhythm < 55 bpm, and poor left ventricular contractility [5]. Endocardial fibroelastosis (EFE), myocarditis, dilated cardiomyopathy, and valvar insufficiency may represent other manifestations of autoimmune disease.

Pregnancy surveillance
Screening for CHB in anti-SSA-positive pregnancy consists of weekly echocardiograms performed between 16 and 26 weeks of gestation. Measurement of atrioventricular intervals to determine first degree block may be done both by pulsed Doppler (PD) and tissue Doppler imaging (TDI), although cut-offs for these values depend on type and place of measurement as well as on gestational age [6]. Higher grades of block may be visualized both with M-mode and Doppler technique (Figure 1).
Studies show that AV prolongation measurement has little value for CHB prediction later in pregnancy [7]. Furthermore, complete heart block in majority of cases is not proceeded by first or second degree block and can develop rapidly (even within 24 hours) in anti-SSA-affected pregnancy.
This was confirmed in the PRIDE study by Friedman et al. in 2008 [8], which enrolled 127 anti-SSA-positive women, 95 of whom completed an evaluation based on weekly echocardiograms from 16 to 26 weeks of gestation and biweekly from 26 to 34 weeks. PR intervals were measured with a cut-off of 150 ms. The authors concluded that PR prolongation was rare and did not precede more advanced block, which may occur within one week of a normal echocardiogram.
Such potential for a rapid progression of lower degree block and/or de novo appearance of heart block creates a gap when even with the weekly monitoring mentioned above, emergent CHB still can be missed; this is important regarding treatment possibilities (see below) and imposes research on other diagnostic tools.
Fetal heart rate and rhythm monitoring (FHRM) is a self-evaluation method using a handheld Doppler, based on evaluation every 12 hours by pregnant women. If any abnormality in fetal heart rate is discovered, prompt detailed heart evaluation and therapy is offered. A prospective study by Cuneo et al. confirmed that FHRM can be used do catch atrioventricular block occurrence in a time frame allowing effective therapy. 87% of mothers who took part in the study completed the protocol. Three second or third degree blocks were discovered, and with therapy started in less than 12 hours second degree blocks were converted to sinus rhythm, and most importantly, no AVB was missed during the FHRM protocol [9, 10].

Prevention of CHB in subsequent pregnancies of anti-SSA-positive mothers
The risk of recurrence of CHB is about 19%. The role of macrophage toll-like receptors as factors contributing to immune-mediated CHB is currently emphasized. Therefore, a well-known medication acting as a toll-like receptor antagonist, hydroxychloroquine (HCQ), is tested for this purpose, with promising results so far. A multicentre, single-arm, 2-stage clinical trial by Izmirly et al. [11, 12] recruited anti-SSA-positive mothers who previously had a CHB-affected child (n = 19 stage 1, n = 35 stage 2), with HCQ implemented in early pregnancy (started before 10th week, 400 mg daily, maintained during pregnancy), which proved that HCQ can reduce the risk of block recurrence by over 50%.
The authors concluded that HCQ should be prescribed to prevent recurrence of CHB. (Preventive Approach to Congenital Heart Block with Hydroxychloroquine [PATCH]; NCT01379573). Hydroxychloroquine is well tolerated but potentially contributes to QT prolongation both in mother and in the fetus, especially when co-administered with other medications affecting QT interval (antihistamines etc.). ECG surveillance of the mother and magnetocardiography (not available in Poland) of the fetus play a role in QT-interval monitoring.
As mentioned above, considering the main role of anti-SSA/Ro antibodies in the pathogenesis of heart block [13-15], HCQ should be prescribed to pregnant women with high levels of anti-SSA. Low-titre anti-SSA- or anti-SSB-positive women qualify as a low-risk population, in whom therapy with HCQ requires further investigation and by now should be prescribed for other medical indications (e.g. active disease in the mother).
Preventive therapies in subsequent pregnancies of anti-SSA-positive mothers with immunoglobulins, plasmapheresis (to decrease serum autoantibody levels), and corticosteroids used in different combinations, presented over the years showed conflicting results [16, 17]. Adverse effects of these therapeutic strategies and lack of strong evidence for effectiveness do not support clinical recommendation. Table 1 presents summary of CHB prevention in anti-SSA affected pregnancy.

Beta-mimetics
Salbutamol (up to 3 × 10 mg daily) may be introduced when significant bradycardia (< 50-60 bpm) appears. The heart rate acceleration usually is not significant, we should rather say salbutamol prevents further reduction in ventricular rate, which allows prolongation of pregnancy. By increasing stroke volume, it prevents heart dysfunction as the fetal circulatory reserve is highly dependent on heart rate [18, 19]. However, no improvement in survival rates regarding this medication has been noted. Both before initiation and during treatment with salbutamol, levels of electrolytes and an ECG should be obtained.

Anti-inflammatory and immunomodulating therapy
Fluorinated steroids (oral dexamethasone 4-8 mg per day or betamethasone 3 mg per day) have the ability to cross the placenta, and their anti-inflammatory properties have undergone thorough investigation. Given the well-known side effects both to the mother (hypertension, diabetes) and the fetus (oligohydramnios, growth restriction) as well as divergent data regarding efficacy, especially when used alone, this treatment remains controversial. Meta-analyses suggest that steroids do not prevent AVB progression (all types of blocks analysed together), improve survival, or delay pacemaker implantation [20-24].
Intravenous immunoglobulins (IVIG) reduce the level of autoantibodies and increase the level of anti-inflammatory factors, often prescribed in combination with steroids. Although actual doses (and maximum doses) and duration of treatment are yet to be established, we know that IVIG crosses the placenta, especially in the third trimester, but no significant side effects to the fetus have been observed. Standard precautions when using IVIG in pregnant women (regarding volume overload, haemolysis, thromboembolic complication) should be applied.
An observational study by Cuneo et al. [25] points out that early detection (within 12 hours of AVB occurrence) and urgent treatment of second degree block with corticosteroids and/or IVIG (1 g/kg) may lead to regression or even reverse fetus back to a sinus rhythm. Moreover, in rare cases of acute third degree block, regression after combined therapy (IVIG + steroids) has been observed [26], but in general this type of block, because of irreversible fibrosis and calcification of the AV node, is considered permanent despite all treatment options [27].
Co-administration of steroids and IVIG (1 g/kg every 3 weeks) might be an option for immune-mediated cardiomyopathy/EFE [28], severe ventricular dysfunction, and hydrops fetalis, but the efficacy of this therapy is not proven [29].
Based on data published in recent years by prenatal centres, steroid therapy (±IVIG) in second degree heart block (regardless its duration) is used by most authors and so far cannot be disadvised despite the fact that not all cases will respond to the treatment and some cases will revert to sinus rhythm without medication [30-44]. Further investigation of this subject is necessary.
Tables 2 and 3 present the summary of the medications reported in fetal complete heart block.
Based on the data from Polish National Registry of Fetal Cardiac Anomalies in the years 2004-2017 (Figure 2), yearly we observed from one to 13 fetuses with complete heart block, in the majority with normal heart anatomy [45]. In our referral centre we have 1-4 such cases per year, and therefore, since 2007, we have developed also our institutional policy in perinatal care of fetuses with complete heart block and normal heart anatomy. This policy is very similar to the one presented above but with one major difference. In the case of fetal complete heart block, normal heart anatomy, normal fetal biometry, normal fetal placental thickness, and congestive heart failure (fetal heart cardiomegaly, tricuspid and mitral regurgitation, pericardial effusion, ascites, myocardial hypocontractility) we used also transplacental digoxin to prevent further deterioration and fetal demise. The treatment was carried out in hospital, with the first dose of digoxin at 0.5 mg and afterwards 0.25 mg every 8 hours administered intravenously for 3 days, followed by 0.25 mg every 8 hours orally until delivery/fetal demise. We had success in 2/3 of cases (there was one fetal demise at 32 weeks of gestation), and 2 live-born neonates; one of them required a pacemaker during the first week of postnatal life, and the other one was pacemaker free for 3 months. To observe any improvement in fetal echocardiography, usually 2-3 weeks of maternal transplacental treatment was required. The similar observations were reported by Eronen et al. in 2001 (from Helsinki) [46] and by Brackley et al. in 2000 (from Birmingham, UK) [47]. Also, such treatment in fetuses with complete heart block was recommended by two Japanese centres (Ishikawa et al. 1992 [48], Fukushige et al. 1998 [49]). Digoxin was used even in a twin pregnancy without any side effects (Czeszyńska et al. 1998 [50]).
Review of treatment recommendations for fetuses with immune-mediated complete heart block at the Department of Prenatal Cardiology is presented in Table 4.

Fetal pacing
To date, in utero pacing strategies have been unsuccessful because of the invasive techniques needed to deliver the systems and because of lead displacement issues. A study on a less invasive approach with micropacemaker device deployed in pericardial space is expected to start soon in Los Angeles [20] and hopefully will be an option for fetal hydrops and cases in which medication has failed. Similar devices are already successfully used in adults and on a smaller scale in paediatric patients.
The take-home messages are as follows:
Hydroxychloroquine is used in the prevention of recurrence of CHB in anti-SSA-affected pregnancies and is effective when started before the 10th week of gestation.
Treatment of first degree block is controversial because of rare progression to CHB and adverse effects of treatment.
For second degree heart block, corticosteroids ±IVIG are recommended by most authors because of its progressive potential and documented cases of regression when treated early.
Complete heart block is considered permanent. Due to irreversible fibrosis and calcification of the AV node there are no therapeutic options available. Only emergent CHB (within 12 hours of appearance), assuming inflammation as a potentially reversible state, may be an indication for treatment (steroids + IVIG).
For EFE and severe heart dysfunction in the course of CHB, dexamethasone ±IVIG therapy may be offered.
Severe fetal bradycardia (< 55-60 bpm) may be addressed with β-mimetics to maintain the ventricular rate within a safe range rather than increase it significantly, and to avoid heart failure.
Delivery of a fetus with complete heart block should take place as late as possible (preferably after 37 weeks of gestation), in a tertiary centre, with paediatric cardiology and pacing facilities.

Conclusions

Fetal complete heart block, due to its high morbidity and mortality rate, remains a challenge. Treatment strategies vary among institutions and are strongly limited by the adverse effects of the medication used. Meticulous supervision of pregnancies at risk of AVB and with AVB is necessary, and management based on progression of the disease should be implemented.

Conflict of interest

The authors declare no conflict of interest.

References

1. Sonesson SE, Ambrosi A, Wahren-Herlenius M. Benefits of fetal echocardiographic surveillance in pregnancies at risk of congenital heart block: single-center study of 212 anti-Ro52-positive pregnancies. Ultrasound Obstet Gynecol 2019; 54: 87-95.
2. Wainwright B, Bhan R, Trad C, Cohen R, Saxena A, Buyon J, et al. Autoimmune-mediated congenital heart block. Best Pract Res Clin Obstet Gynaecol 2020; 64: 41-51.
3. Brito-Zeron P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol 2015; 11: 301-312.
4. Skog A, Lagnefeldt L, Conner P, Wahren-Herlenius M, Sonesson SE. Outcome in anti-Ro/SSA-positive pregnancies and population – based incidence of congenital heart block. Acta Obstet Gynecol Scand 2016; 95: 98-105.
5. Eliasson H, Sonesson SE, Sharland G, Granath F, Simpson JM, Carvalho JS, et al.; Fetal Working Group of the European Association of Pediatric Cardiology. Isolated atrioventricular block in the fetus: retrospective, multinational, multicenter study of 175 patients. Circulation 2011; 124: 1919-1926.
6. Nii M, Hamilton RM, Fenwick I, Kingdom JC, Roman KS, Jaeggi ET. Assessment of fetal atrioventricular time intervals by tissue Doppler and pulse Doppler echocardiography: normal values and correlation with fetal electrocardiography. Heart 2006; 92: 1831-1837.
7. Jaeggi ET, Silverman ED, Laskin C, Kingdom J, Golding F, Weber R. Prolongation of the atrioventricular conduction in fetuses exposed to maternal anti-Ro/SSA and anti-La/SSB antibodies did not predict progressive heart block. A prospective observational study on the effects of maternal antibodies on 165 fetuses. J Am Coll Card 2011; 57: 1487-1492.
8. Friedman DM, Kim MY, Copel JA, Davis C, Phoon CK, Glickstein Js, et al. PRIDE investigators. Utility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval an Dexamethasone Evaluation (PRIDE) prospective study. Circulation 2008; 117: 485-493.
9. Cuneo BF, Sonesson SE, Levasseur S, Moon-Grady AJ, Krishnan A, Donofrio MT et al. Home monitoring for fetal heart rhythm during anti-Ro pregnancies. J Coll Cardiol 2018; 72: 1940-1951.
10. Cuneo BF, Moon-Grady AJ, Sonesson SE, Levasseur S, Hornberger L, Donofrio MT, et al. Heart sounds at home: Feasibility of an ambulatory fetal heart rhythm surveillance program for anti-SSA positive pregnancies. J Perinatol 2017; 37: 226-230.
11. Izmirly P, Kim M, Friedman DM, Costedoat-Chalumeau N, Clancy R, Copel JA, et al. Hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti-SSA/Ro-positive mothers. J Am Coll Cardiol 2020; 76: 292-302.
12. Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, Khamasta MA, Kim MY, Saxena A, et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-associated cardiac manifestations of neonatal lupus. Circulation 2012; 126: 76-82.
13. Strasburger JF, Wacker-Gussmann A. Congenital heart block in subsequent pregnancies of SSA/Ro-positive mothers. J Am Coll Cardiol 2020; 76: 303-305.
14. Jaeggi E, Laskin C, Hamilton R, Kingdom J, Silverman E. The importance of the level of maternal anti-Ro/SSA antibodies as a prognostic marker of the development of cardiac neonatal lupus erythematosus a prospective study of 186 antibody-exposed fetuses and infants. J Am Coll Cardiol 2010; 55: 2778-2784.
15. Anami A, Fukushima K, Takasaki Y, Sumida T, Waguri M, Wake N, et al. The predictive value of anti-SSA antibodies titration in pregnant women with fetal congenital heart block. Modern Rheumatol 2013; 23: 653-658.
16. Friedman DM, Llanos C, Izmirly PM, Brock B, Byron J, Copel J, et al. Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block. Results of a multicenter, prospective, open label clinical trial. Arthritis Rheum 2010; 62: 1138-1146.
17. Pisoni CN, Brucato A, Ruffatti A, Espinosa G, Cervera R, Belmonte-Serrano M, et al. Failure of intravenous immunoglobulin to prevent congenital heart block: findings of a multicenter, prospective, observational study. Arthritis Rheum 2010; 62: 1147-1152.
18. Jaeggi E, Ohman A. Fetal and neonatal arrhythmias. Clin Perinatol 2016; 43: 99-112.
19. Jaeggi ET, Fouron JC, Silverman ED, Ryan G, Smallhorn J, Hornberger LK. Transpalcental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 2004; 110: 1542-1548.
20. Izmirly PM, Saxena A, Sahl SK, Shah U, Friedman DM, Kim MY, et al. Assessment of fluorinated steroids to avert progression and mortality in anti-SSA/Ro associated cardiac injury limited to the fetal conduction system. Ann Rheum Dis 2016; 75: 1161-1165.
21. Van den Berg NW, Slieker MC, van Beynum IM, Bilardo CM, de Bruijn D, Clur SA, et al. Fluorinated steroid do not improve outcome of isolated atrioventricular block. Int J Cardiol 2016; 225: 167-171.
22. Michael A, Radwan AA, Ali AK, Abd-Elkariem AY, Shazly SA. Use of antenatal fluorinated corticosteroids in management of congenital heart block: systematic review and meta-analysys. Eur J Obstet Gynecol Reprod Biol 2019; 4: 100072.
23. Friedman DM, Kim MY, Copel JA, Llanos C, Davis C, Buyon JP. Prospective evaluation of fetuses with autoimmune-associated congenital heart block followed in the PR Interval and Dexamethasone Evaluation (PRIDE) study. Am J Cardiol 2009: 103: 1102-1106.
24. Hoxha A, Mattia E, Zanetti A, Carrara G, Morel N, Costedoat-Chalumeau N, et al. Fluorinated steroids are not superior to any treatment to ameliorate the outcome of autoimmune mediated congenital heart block: a systematic review of the literature and meta-analysis. Clin Exp Rheumatol 2020; 38: 783-791.
25. Cuneo BF, Ambrose SE, Tworetzky W. Detection and successful treatment of emergent anti-SSA-mediated fetal atrioventricular block. Am J Obstet Gynecol 2016; 215: 527-528.
26. Friedman DM, Rupel A, Glickstein J, Buyon JP. Congenital heart block in neonatal lupus: the pediatric cardiologist’s perspective. Indian J Pediatr 2002; 69: 517-522.
27. Brucato A, Tincani A, Fredi M, Breda S, Ramoni V, Morel N, et al. Should we treat congenital heart block with fluorinated corticosteroids? Autoimmun Rev 2017; 16: 1115-1118.
28. Trucco SM, Jaeggi E, Cuneo B, Moon-Grady AJ, Silverman E, Silverman N, et al. Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomiopathy. J Am Coll Cardiol 2011; 57: 715-723.
29. Veduta A, Panaitescu AM, Ciobanu AM, Neculcea D, Popescu MR, Peltescu G, et al. Treatment of fetal arrhythmias. J Clin Med 2021; 10: 2510.
30. Fesslova V, Vignati G, Brucato A, De Sanctis M, Butera G, Pisoni MP, et al. The impact of treatment of the fetus by maternal therapy on the fetal and postnatal outcomes for fetuses diagnosed with isolated complete atrioventricular block. Cardiol Young 2009; 19: 282-290.
31. Ciardulli A, D’Antonio F, Magro-Maloso ER, Manzoli L, Anisman P, Saccone G et al. Maternal steroid therapy for fetuses with second-degree immune-mediated congenital atrioventricular block: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 2018; 97: 787-794.
32. Donofrio MT, Moon-Grady AJ, Hornberger KL, Copel JA, Sklansky MS, Abuhamad A, et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation 2014; 129: 2183-2242.
33. Ruffatti A, Cerutti A, Favaro M, Del Ross T, Calligaro A, Hoxha A, et al. Plasampheresis, intravenous immunoglobiluns and bethametasone – a combined protocol to treat autoimmune congenital heart block: a prospective study. Clin Exp Rheumatol 2016; 34: 706-713.
34. Clowse ME, Eudy AM, Kiernan E, Williams MR, Bermas B, Chakravarty E, et al. The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices. Rheumatol 2018; 57 (suppl. S5): v9-v17.
35. Liao H, Tang C, Qiao L, Zhou K, Hua Y, Wang C, et al. Prenatal management strategy for immune – associated congenital heart block inn fetuses. Front Cardiovasc Med 2021; 8: 644122.
36. Carvalho-Carrilho M, Bravo-Valenzuela NJ, Araujo EJ. Congenital complete atrioventricular heart block in a pregnant woman with sjogren syndrome: prenatal care follow-up and the challenge of intrauterine treatment. Rev Bras Ginecol Obstet 2020; 42: 228-232.
37. De Carolis S, Garufi C, De Carolis MP, Botta A, Tabacco S, Salvi S. Autoimmune congenital heart block: a review of biomarkers and managment of pregnancy. Front Pediatr 2020; 8: 607515.
38. Hansahiranwadee W. Diagnosis and management of fetal autoimmune atrioventricular block. J Womens Health 2020; 12: 633-639.
39. Hunter LE, Simpson JM. Atrioventricular block during fetal life. J Saudi Heart Assoc 2015; 27: 164-178.
40. Zhou KY, Hua YM. Autoimmune-associated congenital heart block: a new insight in fetal life. Chin Med J 2017; 130: 2863-2871.
41. Murlewska J, Preis K, Słodki M, Strzelecka I, Smolewska E, Respondek-Liberska M. Management in maternal autoantibody-mediated clinical fetal myocardial disease. Prenat Cardio 2019; 9: 5-11.
42. Di Mauro A, Caroli Casavola V, Guarnieri GF, Calderoni G, Cicinelli E, Laforgia N. Antenatal and postnatal combined therapy for autoantibody – related congenital atrioventricular block. BMC Pregnancy Childbirth 2013; 13: 220.
43. Yuan SM. Fetal arrhythmias: surveillance and management. Hellenic J Cardiol 2019; 60: 7281.
44. Preutz JD, Miller JC, Loeb GE, Silka MJ, Bar-Cohen Y, Chmait RH. Prenatal diagnosis and management of congenital complete heart block. Birth Defects Res 2019; 111: 380-388.
45. Kordjalik P. Analiza wybranych danych z Ogólnopolskiego Rejestru Patologii Kardiologicznych u Płodu z lat 2004–2017 [Selected data from National Polish Registry of Fetal Cardiac Pathology]. Doctoral thesis. Polish Mother’s Memorial Hospital Research Centre, Lodz 2018.
46. Eronen M, Heikkilä P, Teramo K. Congenital complete heart block in the fetus: hemodynamic features, antenatal treatment, and outcome in six cases. Pediatr Cardiol 2001; 22: 385-392.
47. Brackley KJ, Ismail KM, Wright JG, Kilby MD. The resolution of fetal hydrops using combined maternal digoxin and dexamethasone therapy in a case of isolated complete heart block at 30 weeks gestation. Fetal Diagn Ther 2000; 15: 355-358.
48. Ishikawa S, Yin J, Maeda H, Satoh S, Takeuchi A, Yasui H, Koyanagi T, Nakano H. [Successful intrauterine digoxin therapy for fetal complete atrioventricular block with endocardial cushion defect: a case report]. Fukuoka Igaku Zasshi 1992; 83: 315-318.
49. Fukushige J, Takahashi N, Igarashi H, Nakayama H, Inoue K, Hijii T. Perinatal management of congenital complete atrioventricular block: report of nine cases. Acta Paediatr Jpn 1998; 40: 337-340.
50. Czeszyńska MB, Wegrzynowski J, Czajkowski Z, Dawid G. Fetal and neonatal arrhythmia in one of the twins-a case history. Acta Genet Med Gemellol (Roma) 1998; 47: 197-200.
This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2022 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.