The Open Autoimmunity Journal, 2010, 2, 1-10 1 1876-8946/10 2010 Bentham Open Open Access Which Intrauterine Treatment for Autoimmune Congenital Heart Block? S. De Carolis*, S. Salvi, A. Botta, S. Santucci, C. Martino, S. Garofalo and S. Ferrazzani Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy Abstract: Autoimmune Congenital Heart Block (CHB) is considered an immune mediated manifestation, caused by the action of maternal autoantibodies anti-Ro/SSA and anti-La/SSB on fetal cardiac tissues. The incidence of CHB is 2% in anti-Ro/SSA positive women, 3% when both anti-Ro/SSA and anti-La-SSB are positive. In the subsequent pregnancies the risk of recurrence is 9 times higher. The antenatal diagnosis of CHB is possible by the measurement of the “mechanical” PR interval with fetal echocardiogra- phy. When CHB is diagnosed, an intrauterine therapy is possible to increase the atrioventricular conduction speed and im- prove the fetal outcome. Authors recommend maternal treatment with fluorinated steroids, as Dexamethasone or Betamethasone, which reduce the antibody-mediated inflammatory damage of nodal tissue. Other possibilities are the maternal administration of beta- sympathomimetics, in order to increase the fetal heart rate. In the last years three cases of complete CHB in infants of women affected by autoimmune disease were treated in our centre. They were treated in utero with the maternal administration of Betamethasone 4 mg/day soon after the diagnosis until delivery. After delivery, all children needed cardiac pacemaker. The long-term outcome is good in all cases. Keywords: Congenital heart block, intrauterine therapy, echocardiography. INTRODUCTION Autoimmune congenital heart block (CHB) is grouped under the heading of Neonatal Lupus Syndrome (NLS) and is considered a model of passively acquired autoimmunity disease. It offers the exceptional opportunity to examine the effector arm of immunity and to define the pathogenicity of an autoantibody in mediating tissue injury [1]. After the first observation in 1983 that sera from nearly all mothers of children with isolated CHB contain specific autoantibodies [2], this disease attracts considerable atten- tion. The study of CHB requires an “integrational” research [3], which attempts to fit clinical and basic observations to- gether: only if the biology of the disease is understood and this knowledge is brought to the clinic, our clinical manage- ment could be improved. This paper is divided into two sections. Initially, we dis- cuss the epidemiology, the pathogenetic cascade, the clinical manifestation and the diagnostic modalities of CHB; sec- ondly, we discuss the therapeutic approach proposed in lit- erature and present our experience. DEFINITION A correct definition of Heart Block (HB) implies a char- acterization of each term we use to define this disease. Each case could be characterized by major categories: the degree of conduction system disease at diagnosis (complete or in- complete), congenital or not congenital, associated with *Address correspondence to this author at the Department of Obstetrics and Gynecology- Catholic University of Sacred Heart- L.go A. Gemelli, 8 – 00168 Rome, Italy; Tel: +390630156774; Fax: +390635510031; E-mail: saradecarolis@libero.it structural anomalies or in absence of anatomical disease (iso- lated). The HB may be divided into categories related to the current degree of functional disease that is complete versus incomplete. The latter category may be further divided into first-degree (Type I), second-degree (Type II) or intermittent third degree (Type II/III). Recently, Brucato et al. [4] proposed this definition of HB as congenital: “an atrioventricular (AV) block is defined as congenital if it is diagnosed in utero, at birth, or within the neonatal period (0-27 days after birth)”. This is a significant advance on the original definition proposed by Yater in 1929: in his definition a slow heart rate, at a young age (nei- ther defined), and with certain named infections excluded, was enough to make the discovery of HB classifiable as con- genital. Subsequently, several advances in fetal echocardi- ography have been made: fetal echocardiography is now a diagnostic procedure of AV block antenatally; in addition, we could now record a postnatal ECG within the first few hours of birth. Then, Yater’s definition is no longer accept- able [5]. Furthermore, more than half of fetuses found to have CHB will have underlying structural congenital heart dis- ease: the commonest forms of congenital heart disease asso- ciated with HB include left atrial isomerism, often with an accompanying atrioventricular septal defect, as well as levo transposition of the great arteries [6]. CHB is then defined “isolated” in the absence of structural heart disease that may be causally related to HB. This CHB with a structurally normal heart is frequently associated with maternal autoanti- bodies to Ro/SSA and La/SSB.