Elsevier

The Lancet Rheumatology

Volume 1, Issue 3, November 2019, Pages e187-e193
The Lancet Rheumatology

Viewpoint
Routine repeated echocardiographic monitoring of fetuses exposed to maternal anti-SSA antibodies: time to question the dogma

https://doi.org/10.1016/S2665-9913(19)30069-4Get rights and content

Summary

In around 1% of exposed pregnancies, anti-Ro/SSA and anti-La/SSB antibodies lead to congenital heart block, the main feature of neonatal lupus syndrome. As such, echocardiographic screening to detect congenital heart block, done every other week from 16 weeks to at least 24 weeks gestation, is widely recommended for anti-SSA-positive pregnant women. Such screening is now routinely done in many centres worldwide. In this Viewpoint, we call this dogma into question for several reasons. Even if congenital heart block is discovered (which is rare), the usefulness of treatment with fluorinated steroids has not been shown, whereas the associated side-effects are well known. The discovery of congenital heart block very early in the pregnancy does not modify obstetric management, and at least 500 ultrasounds are needed to find one case of congenital heart block, which would ultimately be found by other means. Finally, this screening strategy misses most cases of congenital heart block because most affected women are not known to have anti-SSA antibodies, and thus are not screened. Accordingly, except in the context of research protocols, which are certainly needed and are outside the scope of this Viewpoint, overturning the dogma of routine repeated screenings for congenital heart block could save money and health-care staff time and prevent maternal stress without substantial clinical consequences.

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

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.

References (49)

  • A Brucato et al.

    Should we treat congenital heart block with fluorinated corticosteroids?

    Autoimmun Rev

    (2017)
  • NW Van den Berg et al.

    Fluorinated steroids do not improve outcome of isolated atrioventricular block

    Int J Cardiol

    (2016)
  • N Morel et al.

    Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus

    Int J Cardiol

    (2017)
  • ET Jaeggi et al.

    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

    (2011)
  • P Brito-Zeron et al.

    The clinical spectrum of autoimmune congenital heart block

    Nat Rev Rheumatol

    (2015)
  • ET Jaeggi et al.

    Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease

    Circulation

    (2004)
  • PM Izmirly et al.

    Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus

    Circulation

    (2011)
  • H Eliasson et al.

    Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients

    Circulation

    (2011)
  • G Guettrot-Imbert et al.

    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

    (2011)
  • C Llanos et al.

    Anatomical and pathological findings in hearts from fetuses and infants with cardiac manifestations of neonatal lupus

    Rheumatology (Oxford)

    (2012)
  • MEB Clowse et al.

    The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices

    Rheumatology (Oxford)

    (2018)
  • SE Sonesson et al.

    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

    (2019)
  • N Costedoat-Chalumeau et al.

    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

    (2004)
  • A Brucato et al.

    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

    (2001)
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