We searched the PubMed database using the search terms “congenital heart block”, “neonatal lupus”, “cardiomyopathy AND anti-SSA OR anti-Ro”, and “endocardial fibroelastosis AND anti-SSA OR anti-Ro” for full English-language publications published up until April 5, 2019.
ViewpointRoutine repeated echocardiographic monitoring of fetuses exposed to maternal anti-SSA antibodies: time to question the dogma
Introduction
Passive transplacental passage of maternal anti-SSA and anti-SSB antibodies can cause neonatal lupus syndrome, which is characterised by cardiac neonatal lupus, skin rash, and, more rarely, haematological, hepatic, or neurological manifestations.1, 2 The main cardiac manifestation is advanced (second or third-degree) congenital heart block (figure 1; video), which is associated with substantial mortality (16–28%) and morbidity (eg, 70–75% require pacemaker implantation by age 10 years).1, 2, 3, 4, 5, 6, 7, 8 Congenital heart block fatality approaches 50% when extranodal disease, which includes endocardial fibroelastosis and dilated cardiomyopathy, is present.5, 6, 7, 9, 10 Histologically, congenital heart block manifests as fibrosis, calcification, and infiltration of macrophages and giant cells into, and sometimes extending beyond, the atrioventricular (AV) node.11
The identification of congenital heart block as early as possible to enable in-utero treatment with fluorinated steroids and thereby reduce morbidity and mortality associated with congenital heart block, has long been a basic precept of the antenatal care of pregnant women with known anti-SSA antibodies. Routine close monitoring by serial echocardiography is thus widespread.12, 13, 14 In this Viewpoint, we call this dogma into question for several reasons, particularly the ineffectiveness of this monitoring practice in identifying cases of congenital heart block, and its poor utility in guiding clinical treatment, given that the only known treatment—administration of fluorinated steroids (dexamethasone or betamethasone)—has not been proven to be effective and therefore, in our opinion, should not be routinely recommended outside of clinical trials. We wish to emphasise that this discussion of routine screening in primary care does not pertain to clinical research in expert centres.
Section snippets
Incidence and timing of autoimmune congenital heart block
Our group has reported that the incidence of congenital heart block in the offspring of mothers with connective tissue diseases and anti-SSA antibodies, but no previous fetuses or children with the condition, is between 1% and 2%.15, 16 A 2015 review of studies that included a total of 823 pregnancies in 705 anti-SSA-positive women with no history of fetal congenital heart block reported that ten fetuses had advanced congenital heart block, a prevalence of 1·2%.1 Incidence of congenital heart
Current recommendations for echocardiographic monitoring
The aim of echocardiography is to detect advanced (third-degree and less frequently second-degree) congenital heart block whether or not it is associated with extranodal manifestations. In some cases, monitoring also aims to measure the AV conduction to detect first-degree congenital heart block.
Serial echocardiograms—done every other week (and under some circumstances weekly)—are recommended for pregnant women with known anti-SSA antibodies, starting at 16 weeks gestation, with a reduction in
Maternal status and congenital heart block
Pregnant women who have a first-time diagnosis of fetal congenital heart block are often asymptomatic or paucisymptomatic; as such, they do not usually receive follow-up for an autoimmune disease until anti-SSA antibodies are found subsequent to the congenital heart block diagnosis.5, 6, 7, 27, 28, 29 A systematic review of underlying maternal autoimmune diseases in 856 mothers with affected fetuses found that more than half of the women were classified as asymptomatic carriers of anti-SSA
Management of advanced congenital heart block
When fetal congenital heart block is discovered, physicians are naturally eager to do something to improve the situation.12 The rationale for treatment of diagnosed congenital heart block (or cardiomyopathy) is to diminish the inflammatory insult and consequent fibrotic reaction, and to reduce or eliminate maternal autoantibodies. Various therapeutic approaches have been reported, including corticosteroids, plasmapheresis, intravenous immunoglobulin (IVIG), B-cell depletion therapies,
Management of first-degree congenital heart block
Both the definition and management of first-degree congenital heart block are even more controversial than that of late-stage disease. In utero prolongation of AV conduction has been defined by different techniques, including fetal kinetocardiography and the measurement of mechanical AV conduction as an in utero substitute for the PR interval, and with different cutoffs (from 2 to 3 SDs).
Most respondents to the survey by Clowse and colleagues12 reported that they would recommend starting
Screening cost-effectiveness and maternal consequences
The cost–utility for three models of congenital heart block screening was analysed in 2019.47 The average cost of weekly screening between 16 weeks and 28 weeks gestation (ie, prenatal standard screening), as recommended by the American Heart Association,26 was US$18 880 per pregnancy. The authors concluded that this commonly used screening strategy is not cost-effective except in situations in which the prevalence of disease is elevated (eg, in a woman with a previously affected fetus).47
An
Proposal for screening in primary care
The primary question addressed by this Viewpoint is how anti-SSA-positive pregnant women should be managed, especially in the primary care setting. Echocardiographic screening to detect congenital heart block, done every other week from 16 weeks to at least 24 weeks gestation, is clearly not a satisfactory nor effective monitoring approach. Unfortunately, there is no evidence to support an alternative protocol. As such, a minimal proposal in primary care might be to first discuss a screening
Future research
Although echocardiographical screening techniques successfully detect congenital heart block, they might not do so sufficiently early for the condition to be reversed. Accordingly, handheld Doppler appears to have substantial potential at a cost of around €30–50 per device. A study from 2018,25 reported on classical echocardiographic monitoring through home Doppler-based screening in 315 anti-SSA-positive women. Four fetuses had first-degree congenital heart block diagnosed by echocardiography,
Conclusion
The additional echocardiograms (6–11 per pregnancy) that are routinely done in anti-SSA antibody-positive women show no abnormality in more than 98% of cases. This procedure very rarely identifies cases of high-degree congenital heart block, for which no treatment has proven effective, and although screening might identify first-degree congenital heart block, these cases might better be left untreated. Moreover, echocardiographic screening cannot detect the vast majority of cases, which occur
Search strategy and selection criteria
References (49)
- et al.
Neonatal lupus syndrome: Literature review
Rev Med Interne
(2015) - et al.
Presentation and prognosis of complete atrioventricular block in childhood, according to maternal antibody status
J Am Coll Cardiol
(2006) - et al.
Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome
Autoimmun Rev
(2015) - et al.
Isolated complete heart block in the fetus
Am J Cardiol
(2015) - et al.
Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela
J Am Coll Cardiol
(2001) - et al.
Pregnancy and contraception in systemic and cutaneous lupus erythematosus
Ann Dermatol Venereol
(2016) - et al.
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) - et al.
Home monitoring for fetal heart rhythm during anti-ro pregnancies
J Am Coll Cardiol
(2018) - et al.
Long-term outcome of mothers of children with complete congenital heart block
Am J Med
(1996) - et al.
A combination therapy protocol of plasmapheresis, intravenous immunoglobulins and betamethasone to treat anti-Ro/La-related congenital atrioventricular block. A case series and review of the literature
Autoimmun Rev
(2013)
Should we treat congenital heart block with fluorinated corticosteroids?
Autoimmun Rev
Fluorinated steroids do not improve outcome of isolated atrioventricular block
Int J Cardiol
Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus
Int J Cardiol
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 Cardiol
The clinical spectrum of autoimmune congenital heart block
Nat Rev Rheumatol
Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease
Circulation
Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus
Circulation
Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients
Circulation
A new presentation of neonatal lupus: 5 cases of isolated mild endocardial fibroelastosis associated with maternal anti-SSA/Ro and anti-SSB/La antibodies
J Rheumatol
Anatomical and pathological findings in hearts from fetuses and infants with cardiac manifestations of neonatal lupus
Rheumatology (Oxford)
The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices
Rheumatology (Oxford)
Benefits of fetal echocardiographic surveillance in pregnancies at risk of congenital heart block: a single centre study of 212 anti-Ro52 positive pregnancies
Ultrasound Obstet Gynecol
Outcome of pregnancies in patients with anti-SSA/Ro antibodies: a study of 165 pregnancies, with special focus on electrocardiographic variations in the children and comparison with a control group
Arthritis Rheum
Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women
Arthritis Rheum
Cited by (21)
French national diagnostic and care protocol for Sjögren's disease
2023, Revue de Medecine InterneGlomerular diseases in pregnancy: pragmatic recommendations for clinical management
2023, Kidney InternationalCitation Excerpt :In the presence of antiphospholipid syndrome, aspirin should be added to heparin129 whenever possible during the preconception period to prevent fetal loss, placental insufficiency, and thrombotic complications. Furthermore, in the presence of anti-Ro/SSA antibodies, systematic fetal heart rhythm monitoring is usually advised for early detection of fetal atrioventricular block (detected in 1%–2% of anti-Ro/SSA pregnancies).135–137 Routine screening, however, has recently been challenged and may be reserved for patients with a history of congenital heart block.137
Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers
2022, American Journal of Obstetrics and GynecologyCitation Excerpt :The thresholds we reported have 100% NPV for f-AVB only; it is unclear whether these thresholds would demonstrate high NPV for extranodal disease without conduction system disease. However, isolated extranodal disease is a rare occurrence,17,18 and there is no large study documenting its natural history. Another limitation is that although hydroxychloroquine did not lead to significant differences in median titer levels, it may alter the risk of f-AVB; therefore, treated subjects may have higher titer levels that may indicate increased risk while being born without the disease.
Systemic lupus erythematosus and pregnancy: Strategies before, during and after pregnancy to improve outcomes
2021, Revista Colombiana de ReumatologiaCitation Excerpt :Congenital heart block is usually preceded by lower degrees of conduction delays that can be reversed with early treatment. Close monitoring of anti-SSA/Ro and/or anti-SSB/La positive pregnant women with serial fetal echocardiography between 16 and 26 weeks of gestation is recommended.13,14,87 Detection of an early conduction defect such as a prolonged PR interval should be considered a danger signal.
Home fetal heart rate monitoring in anti Ro/SSA positive pregnancies: Literature review and case report
2021, European Journal of Obstetrics and Gynecology and Reproductive BiologyCitation Excerpt :Unfortunately, this therapy doesn’t successfully reduce the degree of block once complete AV dissociation has been reported. Moreover, side effects of high dose fluorinated steroids during pregnancy should be considered, such as increased blood pressure, osteopenia, osteonecrosis, susceptibility to infections, gestational diabetes, premature rupture of the membranes and oligohydramnios [10,12,32,33]. Actually, there is debate regarding the treatment for each degree of heart block and the prophylactic medication in the first‐degree block.