From an immunologic perspective, elimination of candidate maternal autoantibodies and reduction of a generalized inflammatory response is the logical approach to the treatment of fetal AV block. Relevant to treating fetal disease, dexamethasone, a glucocorticoid agonist which crosses cell membranes, is only partially metabolized by placental 11β-hydroxysteroid dehydrogenase (11β-OHSD) with the remainder available to the fetus in an active form. The same is not true of prednisone, which does not transfer to the fetus. Dexamethasone binds with high affinity to specific cytoplasmic receptors which modify transcription and resultant protein synthesis to inhibit leukocyte infiltration at the site of inflammation. Dexamethasone thus interferes in the function of the mediators of the inflammatory response.¹⁹

IVIG treatment has been of benefit in a variety of immune-mediated and inflammatory diseases in pregnant women and pediatric patients.²⁰ It is approved by the Federal Drug Administration for primary immunodeficiency, idiopathic thrombocytopenia purpura, Kawasaki disease, B cell-chronic lymphocytic leukemia with hypogammaglobulinemia, pediatric HIV infection, and allogenic bone marrow transplant in adults.²⁰ The major rationale for IVIG in the treatment of AV block was initially based on elimination of anti-Ro antibodies: “no antibody, no disease.”²¹,²² However, it remains highly speculative whether IVIG can effectively lower the level below the threshold needed to result in cardiac injury. We know that replacement doses of IVIG at 400 mg/kg do not prevent recurrence of fetal AV block.² However, in mice at doses of 1 gm/kg, IVIG is immunomodulatory via IgG-Fc sialylation and increased surface expression of the inhibitory FcγRIIb receptor on macrophages.²³ Data in humans support that IVIG inhibits phagocytosis of IgG-opsonized blood cells (in the case of AV block predicted to be cardiocytes opsonized by anti-Ro independent of Ig-Fc sialylation).²²,²³ Clinical results in anecdotal reports have suggested IVIG improves outcome in cardiomyopathy²⁴ (TABLE 4.3.1), but it has not been evaluated as an adjunct treatment with dexamethasone for AV block with normal cardiac function.

Although expensive, IVIG may be an effective drug if used in treatment of emerging 3° AV block, especially in combination with dexamethasone.²⁵,²⁶,²⁷,²⁸,²⁹ However, whether monthly doses during pregnancy or postnatal treatment is required, is unknown and proof for any rationale is lacking. We await the results of future prospective studies to develop an evidence-based treatment plan for these high-risk fetuses.