Abstract
Introduction/objectives
Complete congenital atrioventricular block (AVB) may be due to cardiac malformations or the presence of maternal antibodies (autoimmune AVB). Our objective was to estimate the prevalence of autoimmune AVB among all AVB in newborns treated at our hospital. Secondly, we estimated the prevalence of AVB among mothers with anti-Ro/La antibodies and examined the relationship of those fetal AVB with mother’s use of hydroxychloroquine during pregnancy.
Methods
Retrospective cohort in which we reviewed electronic medical records from years 2000 to 2014 of (a) all mothers with children born with third degree AVB and (b) all pregnant women with anti-Ro/La-positive antibodies.
Results
Twenty-three AVBs were diagnosed. Ten (43.5%, 95% CI 23.2–65.5) were associated with maternal rheumatologic disease. The remaining 13 were associated with cardiac malformations. Sixty-two pregnancies in 47 mothers with Ro/La antibodies were identified; eight (12.9%, 95% CI 5.7–23.8) suffered AVB. Fourteen mothers consumed hydroxychloroquine during full pregnancy (one newborn (7.1%) suffered AVB) and 48 did not (7 newborns with AVB (14.6%); p = 0.5).
Conclusions
All congenital AVB diagnosed at our hospital without cardiac malformations were associated with a maternal rheumatologic disease/antibodies. Therefore, if a AVB is diagnosed in a newborn without structural heart disease, the mother should be studied for an autoimmune disease. We found a high prevalence of AVB among mothers with anti-Ro/La antibodies. Although not statistically significant, AVBs in mothers with Ro/La antibodies were numerically more frequent in those not using hydroxychloroquine.
Key Points • Although structural heart malformations were the predominant cause of third-degree AVB, autoimmune AVB was still a significant cause. • The distinction between structural or non-structural cause of AVB constitutes an essential issue since it determines the prognostic of these fetuses in terms of complications. • Although not statistically significant, AVBs in mothers with Ro/La antibodies were more frequent in those not using hydroxychloroquine. • If an AVB is diagnosed in a newborn without structural heart disease, the mother should be studied for an autoimmune disease. |
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References
Buyon JP, Waltuck J, Kleinman C, Copel J (1995) In utero identification and therapy of congenital heart block. Lupus 4:116–121
Buyon JP (1996) Neonatal lupus: bedside to bench and back. Scand J Rheumatol 25:271–276
Buyon JP, Hiebert R, Copel J, Craft J, Friedman D, Katholi M, Lee LA, Provost TT, Reichlin M, Rider L, Rupel A, Saleeb S, Weston WL, Skovron ML (1998) Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol 31:1658–1666
Brucato A, Cimaz R, Caporali R, Ramoni V, Buyon J (2011) Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies. Clin Rev Allergy Immunol 40:27–41. https://doi.org/10.1007/s12016-009-8190-6
Wojakowski A, Izbizky G, Carcano ME, Aiello H, Marantz P, Otaño L (2009) Fetal Doppler mechanical PR interval: correlation with fetal heart rate, gestational age and fetal sex. Ultrasound Obstet Gynecol 34:538–542. https://doi.org/10.1002/uog.7333
Friedman DM, Kim MY, Copel JA, Davis C, Phoon CKL, Glickstein JS, Buyon JP (2008) Utility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval and Dexamethasone Evaluation (PRIDE) prospective study. Circulation 117:485–493. https://doi.org/10.1161/CIRCULATIONAHA.107.707661
Buyon JP, Clancy RM, Friedman DM (2009) Cardiac manifestations of neonatal lupus erythematosus: guidelines to management, integrating clues from the bench and bedside. Nat Clin Pract Rheumatol 5:139–148. https://doi.org/10.1038/ncprheum1018
Fritsch C, Hoebeke J, Dali H, Ricchiuti V, Isenberg DA, Meyer O, Muller S (2006) 52-kDa Ro/SSA epitopes preferentially recognized by antibodies from mothers of children with neonatal lupus and congenital heart block. Arthritis Res Ther 8:R4. https://doi.org/10.1186/ar1848
Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, Khamashta MA, Kim MY, Saxena A, Friedman D, Llanos C, Piette JC, Buyon JP (2012) Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 126:76–82. https://doi.org/10.1161/CIRCULATIONAHA.111.089268
Mollerach FB, Scolnik M, Rosa J, Catoggio LJ, Soriano ER Cohort of pregnant women with Ro/La antibodies: risk of fetal third degree atrioventricular block and use of hydroxychloroquine - ACR Meet. https://acrabstracts.org/abstract/cohort-of-pregnant-women-with-rola-antibodies-risk-of-fetal-third-degree-atrioventricular-block-and-use-of-hydroxychloroquine/. Accessed 3 July 2018
Chandler SF, Fynn-Thompson F, Mah DY (2017) Role of cardiac pacing in congenital complete heart block. Expert Rev Cardiovasc Ther 15:853–861. https://doi.org/10.1080/14779072.2017.1376655
Clowse MEB, Eudy AM, Kiernan E, Williams MR, Bermas B, Chakravarty E, Sammaritano LR, Chambers CD, Buyon J (2018) The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices. Rheumatology 57:v9–v17. https://doi.org/10.1093/rheumatology/key141
Eddy WA, Frankenfeld RH (1977) Congenital complete heart block in pregnancy. Am J Obstet Gynecol 128:223–225. https://doi.org/10.1016/0002-9378(77)90695-0
Evers PD, Alsaied T, Anderson JB, Cnota JF, Divanovic AA (2018) Prenatal heart block screening in mothers with SSA/SSB autoantibodies: targeted screening protocol is a cost-effective strategy. Congenit Heart Dis 14:221–229. https://doi.org/10.1111/chd.12713
Levy R, Vilela V, Cataldo M et al (2001) Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 10:401–404. https://doi.org/10.1191/096120301678646137
Clowse MEB, Magder L, Witter F, Petri M (2006) Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 54:3640–3647. https://doi.org/10.1002/art.22159
Pons-Estel GJ, Catoggio LJ, Cardiel MH, Bonfa E, Caeiro F, Sato E, Massardo L, Molina-Restrepo JF, Toledano MG, Barile-Fabris LA, Amigo MC, Acevedo-Vásquez EM, Abadi I, Wojdyla D, Alarcón-Riquelme ME, Alarcón GS, Pons-Estel BA (2015) Lupus in Latin-American patients: lessons from the GLADEL cohort. Lupus 24:536–545. https://doi.org/10.1177/0961203314567753
Izmirly PM, Kim MY, Llanos C, le PU, Guerra MM, Askanase AD, Salmon JE, Buyon JP (2010) Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis 69:1827–1830. https://doi.org/10.1136/ard.2009.119263
Koh JH, Ko HS, Kwok S-K, Ju JH, Park SH (2015) Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus. Lupus 24:210–217. https://doi.org/10.1177/0961203314555352
Martínez-Sánchez N, Pérez-Pinto S, Robles-Marhuenda Á, Arnalich-Fernández F, Martín Cameán M, Hueso Zalvide E, Bartha JL (2017) Obstetric and perinatal outcome in anti-Ro/SSA-positive pregnant women: a prospective cohort study. Immunol Res 65:487–494. https://doi.org/10.1007/s12026-016-8888-5
Izmirly PM, Saxena A, Kim MY, Wang D, Sahl SK, Llanos C, Friedman D, Buyon JP (2011) Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation 124:1927–1935. https://doi.org/10.1161/CIRCULATIONAHA.111.033894
Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, Sánchez-Guerrero J, Wofsy D, Yu X, Solomons N (2010) Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford) 49:128–140. https://doi.org/10.1093/rheumatology/kep346
Allesee L, Gallagher CM (2011) Pregnancy and protection: the ethics of limiting a pregnant woman’s participation in clinical trials. J Clin Res Bioeth 2. https://doi.org/10.4172/2155-9627.1000108
Hutter D, Silverman ED, Jaeggi ET (2010) The benefits of transplacental treatment of isolated congenital complete heart block associated with maternal anti-Ro / SSA antibodies: a review. Scand J Immunol 72:235–241. https://doi.org/10.1111/j.1365-3083.2010.02440.x
Saxena A, Izmirly PM, Mendez B, Buyon JP, Friedman DM (2014) Prevention and treatment in utero of autoimmune-associated congenital heart block. Cardiol Rev 22:263–267. https://doi.org/10.1097/CRD.0000000000000026
Eliasson H, Sonesson S-E, Sharland G, Granath F, Simpson JM, Carvalho JS, Jicinska H, Tomek V, Dangel J, Zielinsky P, Respondek-Liberska M, Freund MW, Mellander M, Bartrons J, Gardiner HM, for the Fetal Working Group of the European Association of Pediatric Cardiology (2011) Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients. Circulation 124:1919–1926. https://doi.org/10.1161/CIRCULATIONAHA.111.041970
Ruffatti A, Milanesi O, Chiandetti L, Cerutti A, Gervasi MT, de Silvestro G, Pengo V, Punzi L (2012) A combination therapy to treat second-degree anti-Ro/La-related congenital heart block. A strategy to avoid stable third-degree heart block? Lupus 21:666–671. https://doi.org/10.1177/0961203311430969
Trucco SM, Jaeggi E, Cuneo B, Moon-Grady AJ, Silverman E, Silverman N, Hornberger LK (2011) Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy. J Am Coll Cardiol 57:715–723. https://doi.org/10.1016/j.jacc.2010.09.044
Friedman DM, Llanos C, Izmirly PM, Brock B, Byron J, Copel J, Cummiskey K, Dooley MA, Foley J, Graves C, Hendershott C, Kates R, Komissarova EV, Miller M, Paré E, Phoon CKL, Prosen T, Reisner D, Ruderman E, Samuels P, Yu JK, Kim MY, Buyon JP (2010) 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 62:1138–1146. https://doi.org/10.1002/art.27308
Pisoni CN, Brucato A, Ruffatti A, Espinosa G, Cervera R, Belmonte-Serrano M, Sánchez-Román J, García-Hernández FG, Tincani A, Bertero MT, Doria A, Hughes GRV, Khamashta MA (2010) Failure of intravenous immunoglobulin to prevent congenital heart block: findings of a multicenter, prospective, observational study. Arthritis Rheum 62:1147–1152. https://doi.org/10.1002/art.27350
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This study was approved by the Clinical Research Ethics Committee of Hospital Italiano de Buenos Aires and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
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Mollerach, F.B., Scolnik, M., Catoggio, L.J. et al. Causes of fetal third-degree atrioventricular block and use of hydroxychloroquine in pregnant women with Ro/La antibodies. Clin Rheumatol 38, 2211–2217 (2019). https://doi.org/10.1007/s10067-019-04556-8
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DOI: https://doi.org/10.1007/s10067-019-04556-8