Maternal autoantibody levels in congenital heart block and potential prophylaxis with antiinflammatory agents

Tunks, Robert D.; Clowse, Megan E.B.; Miller, Stephen G.; Brancazio, Leo R.; Barker, Piers

doi:10.1016/j.ajog.2012.09.020

Cited by 68 publications

(67 citation statements)

References 24 publications

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“…Four out of five case–control studies detected higher levels of anti-Ro52 antibodies in affected than in nonaffected pregnancies, 14,33,46,48 as did two of three studies that tested levels of anti-Ro60 antibodies. 14,48,52 Interestingly, only one study used native antigens for detection, and in this study anti-Ro60 antibodies were significantly higher in mothers either with an affected baby ( P = 0.0002) or with a previous history of affected babies ( P = 0.0001), compared with women with unaffected babies, whereas there was no statistical difference in anti-Ro52 antibody titres. 52 …”

Section: Maternal Featuresmentioning

confidence: 83%

“…In our systematic review of underlying maternal autoimmune diseases, of 856 affected mothers more than half were classified as asymptomatic carriers of anti-Ro and anti-La antibodies, and ~14% were classified as incomplete or undifferentiated autoimmune disease (Figure 4). 16,19,28,48,62–64 The remaining cases were mothers diagnosed with a specific autoimmune disease, almost all with pSS or SLE, or both; only 13 cases were diagnosed with other autoimmune diseases, including five with rheumatoid arthritis. More than half the affected mothers might have been asymptomatic, as anti-Ro and anti-La antibodies can be detected several years before SLE 65 or pSS 66 are diagnosed.…”

Section: Maternal Featuresmentioning

confidence: 99%

“…15,17,22,24,25,28,32,33,40,42,48,62,68,69 However, isolated cases have been reported earlier than 18 weeks; one case was at 16 weeks, 70 one at 17 weeks, 70 and two cases during the third month of pregnancy. 71 In more than half the cases, AV block was diagnosed at 20–24 weeks of gestation, and in 75% was during weeks 20–29.…”

Section: Fetal Features Of Chbmentioning

confidence: 99%

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The clinical spectrum of autoimmune congenital heart block

et al. 2015

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Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder.

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Section: Maternal Featuresmentioning

confidence: 83%

Section: Maternal Featuresmentioning

confidence: 99%

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The clinical spectrum of autoimmune congenital heart block

et al. 2015

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“…Importantly, there is strong evidence that maintaining women with SLE on their antimalarials during pregnancy improves both patient and pregnancy outcomes [ 27 ]. Furthermore, recent evidence suggests that this medication may have a role in secondary prevention of congenital complete heart block (CCHB) in anti-Ro, anti-La positive women who have previously given birth to a child with CCHB [ 28 ]. Hydroxychloroquine may be continued during breastfeeding.…”

Section: Antimalarialsmentioning

confidence: 99%

The Medical Management of the Rheumatology Patient During Pregnancy

Bermas

2014

Contraception and Pregnancy in Patients With Rheumatic Disease

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Congenital anomalies occur in 3 % of normal pregnancies [ 1 ]. Therefore, risk assessment of any particular agent during pregnancy needs to take into account this background rate of teratogenicity. For many years, clinicians relied on the FDA risk categories (A, B, C, D, and X) to assess drugs for safety for use in pregnancy. As Briggs, author of the major textbook in this fi eld, points out, these risk assessments are limited because they are "confusing and simplistic" and incorrectly gave the impression that risk increases from category to category [ 2 ]. The FDA is currently considering new labeling for pregnancy risk. The approach this chapter will take is to present the available data on medication safety in pregnancy and lactation and to synthesize the information regarding drug safety.Each pregnant woman has her own view about assuming risk during her pregnancy. For example, some women will avoid any substance that could have potential risk during pregnancy (caffeine, over-the-counter medications, food-additives) while other women will be willing to assume some risk and modify their ingestion of these substances. Similarly, treating physicians have varying tolerance to risk. While one clinician may be willing to prescribe TNF-α blockers during pregnancy, others will be uncomfortable recommending these medications. Therefore, when approaching management decisions of rheumatic diseases during pregnancy, it is helpful for the treating clinician to be aware of both the patient's and their own risk tolerance, in addition to the available medical data. To this end, up-front discussions prior to conception or early in pregnancy regarding what medications may be used safely and comfortably in the case of a disease fl are are ideal.

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“…49,76 Concerning maternal treatment during pregnancy, the administration of hydroxychloroquine together with a low dose of prednisone might exert protective effects. 77 Other miscellaneous manifestations of NL include hepatobiliary damage, which can be associated with jaundice, cholestatic hepatitis, and occasional thrombocytopenia; anemia; hyperbilirubinemia; and elevated transaminase levels. The hepatic dysfunction occurs in utero or appears shortly after birth, and clinical and biochemical parameters typically return to normal after approximately eight weeks.…”

Section: Ro/ssa Molecular Complexmentioning

confidence: 99%

Pathogenic effects of maternal antinuclear antibodies during pregnancy in women with lupus

2014

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Lupus is an autoimmune disease that primarily affects young women of childbearing age. Fertility rates in lupus patients depend on various factors, including disease activity, nephritis, and the presence of antiphospholipid antibodies; however, after lupus patients become pregnant, different factors may affect the course of pregnancy, such as the production of autoantibodies, pre-existing renal disease, and eclampsia, among others. The placenta is a temporary hemochorial organ that prevents immunological conflict due to exposure to alloantigens at the maternal-fetal interface; placental regulatory T cells play a major role in maternal-fetal tolerance. Typically, significant amounts of maternal IgG class antibodies cross the placenta and enter the fetal circulation. This transition depends on the distribution of Fc receptors along the syncytiotrophoblast. The production of antinuclear antibodies (ANA) is a hallmark of lupus, and these autoantibodies can form immune complexes that are typically trapped in the placenta during gestation. However, the entry of ANA into the fetal circulation depends on the IgG-ANA concentration and the FcR placental density. Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus if transfused by the placental pathway and could induce neonatal pathologies, such as neonatal lupus and congenital heart block. Here, we review the experimental and clinical data supporting a pathogenic role for maternal autoantibodies transmitted to the fetus.

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Maternal autoantibody levels in congenital heart block and potential prophylaxis with antiinflammatory agents

Cited by 68 publications

References 24 publications

The clinical spectrum of autoimmune congenital heart block

The clinical spectrum of autoimmune congenital heart block

The Medical Management of the Rheumatology Patient During Pregnancy

Pathogenic effects of maternal antinuclear antibodies during pregnancy in women with lupus

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