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Introduction Material and Methods Results Conclusions We investigated the effects of timing of detection and transplacental fluorinated steroid treatment on ventricular heart rate (HR) and age at pacemaker implantation in fetal third‐degree atrioventricular block (AVB).Twenty‐five of 31 fetuses diagnosed with Ro/SSA autoantibody‐positive AVB II‐III at our tertiary fetal cardiology center (2000–2020) and AVB III as final feto‐neonatal outcome were reviewed.AVB was detected approximately 5 weeks earlier in pregnancy if followed in a surveillance program compared to cases referred from primary care for bradycardia (20.6 [2.3] [mean (SD)] vs. 25.4 [3.2] weeks, p = 0.001). AVB detected before 24 weeks had higher HR than those detected later in gestation (63.3 [6.9] vs. 57.2 [6.9] bpm, p = 0.042), with a larger proportion having HR >60 bpm (80% vs. 33%, p = 0.041). The 17/25 cases that received treatment with fluorinated steroid were diagnosed earlier in gestation, with higher HR at diagnosis (61.7 [7.1] vs. 54.7 [6.3] bpm, p = 0.026), 1–2 weeks after diagnosis/treatment start, and before birth (65.4 [12.4] vs. 54.9 [5.7] bpm, p = 0.030) than untreated cases. Overall, 11 cases were commenced on betamimetics: three at diagnosis and eight at or after the examination made 1–2 weeks after diagnosis/treatment start, without any HR improvement. Two of 24 surviving babies were born preterm, and 4/24 received a neonatal pacemaker. Age at pacemaker implantation correlated significantly with HR before birth (Spearman R 0.57, p = 0.004), and fetuses with HR >60 bpm had a higher rate of pacemaker‐free survival at three (90% vs. 40%, p = 0.018) and 12 months of age (80% vs. 13%, p = 0.002). The same trend was observed in pacemaker‐free survival at 3 months of age in fluorinated steroid‐treated compared to untreated cases (71% vs. 38%, ns).Our data confirm that AVB III detected earlier in gestation have a higher HR, and suggest that this higher HR can be successfully maintained to the end of gestation in cases treated with fluorinated steroids. Fetuses with HR >60 bpm before birth had a lower rate of pacemaker implantation at 3 and 12 months of age. [ABSTRACT FROM AUTHOR]

Objectives: To determine the clinical course of fetal isolated non‐immune‐mediated second‐degree atrioventricular block (AVB) and the factors associated with spontaneous recovery in these cases. Methods: Fetuses with isolated non‐immune‐mediated second‐degree AVB were recruited prospectively between 2014 and 2022. These fetuses were divided into two groups: those which recovered spontaneously and those which did not. Maternal and fetal characteristics and intrauterine and postnatal outcomes were compared between the two groups. Results: The study cohort included 20 fetuses with isolated non‐immune‐mediated second‐degree AVB, diagnosed at a median gestational age of 22.0 (range, 17.0–35.0) weeks. In 12 fetuses, 1:1 atrioventricular conduction was restored spontaneously in utero and there was no recurrence during the postnatal follow‐up period. In the remaining eight fetuses, second‐degree AVB was maintained and, in six of these, the pregnancy was terminated on parental request. Of the two liveborn children who had persistent second‐degree AVB prenatally, one had progressed to complete AVB at the latest follow‐up, at the age of 34 months, but was asymptomatic, without heart enlargement or dysfunction. The other child progressed to complete AVB after delivery and was diagnosed with type‐2 long QT syndrome. This infant died aged 2 months. Fetuses in the group that recovered spontaneously had earlier gestational age at diagnosis (median, 20.0 (range, 17.0–26.0) vs 24.5 (range, 18.0–35.0) weeks; P = 0.004) and higher atrial rate at diagnosis (median, 147 (range, 130–160) vs 138 (range, 125–149) bpm; P = 0.006) in comparison with the group that did not recover spontaneously. The best cut‐off values for prediction of failure to recover spontaneously were 22.5 weeks' gestational age at diagnosis and 144 bpm atrial rate at diagnosis, with sensitivities of 87.5% and 75.0%, respectively, and specificities of 92.0% and 87.5%, respectively. Conclusions: The outcome of 60% of fetuses with isolated non‐immune‐mediated second‐degree AVB was favorable. Earlier gestational age and higher atrial rate at diagnosis were associated with spontaneous reversion to normal sinus rhythm. Prenatal genetic testing should be performed in cases with persistent AVB, to exclude heritable disorders including long QT syndrome. These findings provide important information for clinical management and prenatal counseling in these cases. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the parents' experiences of home monitoring of the fetal heart rhythm. Women with anti-SSA/Ro52 autoantibodies carry a 2%–3% risk of giving birth to a child with congenital heart block (CHB), following transplacental transfer and antibody-mediated inflammation in the fetal conduction system during 18th to 24th gestational week. Early detection and subsequent treatment have been reported to decrease morbidity and mortality. Therefore, home monitoring of the fetal heart rhythm by Doppler has been offered at our fetal cardiology center. This study was undertaken to explore the lived experience of the routine. Methods: Participants were recruited from a single fetal cardiology center. Consecutive sampling was used. The inclusion criteria were women with SSA/Ro52 antibodies who had undergone Doppler examinations within the last two and a half years at the hospital and had monitored the fetal heartbeat at home. A semi-structured questionnaire was created, and the participants were interviewed individually. The interviews were transcribed verbatim and analyzed according to qualitative content analysis. Results: The overall theme was defined as "walking on thin ice," with six underlying categories: reality, different strategies, gain and loss, healthcare providers, underlying tension, and conducting the examinations again, all with a focus on how to handle the home monitoring during the risk period. Conclusion: Both the mother and the co-parent expressed confidence in their own abilities and that the monitoring provided them with the advantage of growing a bond with the expected child. However, all the participants described a feeling of underlying tension during the risk period. The results show that home monitoring is not experienced as complicated or a burden for the parents-to-be and should be considered a vital part of the chain of care for mothers at risk for giving birth to a child with CHB. However, explaining the teamwork between the different caregivers, for the patients involved, their areas of expertise, and how they collaborate with the patient continues to be a pedagogic challenge and should be developed further. [ABSTRACT FROM AUTHOR]

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants. [ABSTRACT FROM AUTHOR]

Background: It has been reported that the complete heart block (CHB) in neonatal lupus (NL) cannot be reversed. This study reported a case of NL-CHB that was reversed by transcutaneous pacing and repeated plasmapheresis. Case presentation: A 35+ 6-week male preterm baby was transferred to the neonatal intensive care unit of the Army Medical Center in May 2020 for slight cyanosis around the lips and nose. Two days after birth, a sudden decrease in heart rate was observed during electrocardiogram (EGG) monitoring. Physical examination revealed a bluish-purple discoloration around the lips and an irregular heartbeat. EGG showed the presence of isolated P (142 bpm) and QRS (78 bpm) waves, ventricular escape beats, and a diagnosis of NL-CHB. To reverse the condition, transcutaneous pacing and five sessions of plasmapheresis were performed. At a 1.5-year follow-up, the baby exhibited well-developed cardiac structure and normal neurodevelopment. Conclusions: Transcutaneous pacing and repeated plasmapheresis might be possible to reverse CHB in NL. [ABSTRACT FROM AUTHOR]

Background: Chronic right ventricular (RV) apical pacing in patients with congenital complete atrioventricular block (CCAVB) is associated with left ventricle (LV) dyssynchrony and dysfunction. Hence, alternative pacing sites are advocated. The aim of this study was to compare LV function using STE in selected patients with LV epicardial pacing (LVEp) vs. RV transvenous pacing (RVSp). Methods: This was a single-center, retrospective study in patients with CCAVB who underwent permanent pacemaker implant at age ≤ 18 years. Age- and gender-matched patients with a normal heart anatomy and function served as the control group. LV function was comprehensively assessed by conventional 2D Echocardiography and speckle-tracking echocardiography (STE). Results: We included 24 patients in the pacemaker group [27.6% male, mean age of 17.1 at last follow-up, follow-up duration of 8.7 years, RVSp (n = 9; 62.5%)] compared to 48 matched healthy controls. Shortening fraction (SF) and ejection fraction (EF) were normal and similar between cases and controls. However, STE detected abnormal LV function in the pacemaker group compared to controls. The former demonstrated lower/abnormal, Peak Longitudinal Strain myocardial (PLS Myo) [− 12.0 ± 3.3 vs. − 18.1 ± 1.9, p < 0.001] and Peak Longitudinal Strain endocardial (PLS endo) [− 16.1 ± 4.1 vs. 1.7 ± 1.7, p < 0.001]. STE parameters of LV function were significantly more abnormal in LVEp vs. RVSp subgroup as demonstrated by lower values for PLS Myo (− 10.1 ± 3.2 vs. − 13.1 ± 2.9, p = 0.03) and PLS Endo (− 13.8 ± 4.4 vs. − 17.5 ± 3.3, p = 0.03). Conclusion: STE was more sensitive in detecting subtle differences in LV function relative to standard conventional 2D echocardiography (SF and EF) in selected patients with CCAVB and a permanent pacemaker. Furthermore, STE demonstrated that transvenous RV septal pacing was associated with better LV systolic function preservation than LV epicardial pacing for comparable post-implant intervals. [ABSTRACT FROM AUTHOR]

Background: Complete atrioventricular block (CAVB) is a complication of maternal antibody positivity and treatment of fetal disease is controversial in terms of efficacy and safety. We hypothesized that dexamethasone treatment for fetal anti-Ro/SSA antibody-mediated cardiac disease leads to better pregnancy outcomes than expectant management. Methods: A retrospective multi-center cohort study of anti-Ro/SSA antibody positive pregnancies with fetal conduction disease reported by participating North American Fetal Therapy Network (NAFTNet) centers between January 2010 and December 2018. The primary outcomes included: fetal death, oligohydramnios, growth restriction, preterm delivery, and new maternal comorbidities. Secondary outcomes included: pacemaker prior to 28 days, transplantation, and neonatal death in maternal/fetal dyads treated with dexamethasone versus not. Results: In 127 anti-Ro/SSA positive pregnancies, 98 were treated with dexamethasone and 29 were not. Of those treated, 61/96 (63.5%) met the primary outcome including 45/91 (49.4%) premature deliveries; 20 mothers developed comorbidities during treatment (fetal death 5, 10 growth restriction, 14 oligohydramnios, two new/worsening gestational diabetes). In the untreated group, 15/25 (60%) met the primary outcome including 11/22 (50%) premature deliveries and four mothers developing comorbidities during their pregnancy (fetal death 3, one growth restriction, one new onset maternal hypertension). Regarding secondary outcomes, 37/ 96 (43%) treated fetuses required a pacemaker or died by 28 days, while untreated 13/25 (52%) required pacemaker placement, died prior to 28 days or required listing for transplantation. Excluding terminations, survival without transplant was 17 (68%) in untreated and 85 (89%) in treated patients (p<.01). Conclusions: While the use of dexamethasone in anti-Ro/SSA positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was an unexpected similarly high rate in untreated positive pregnancies. This suggests that the maternal disease itself is influencing pregnancy complications independent of dexamethasone. Our data, which show that treatment decreases neonatal morbidity and overall mortality without increasing overall pregnancy complications, warrant further study. [ABSTRACT FROM AUTHOR]

Neonatal lupus erythematosus (NLE) is a congenital autoimmune condition in which the transplacental passage of immunoglobulin G (IgG) directed against auto-antigens causes clinical symptoms in the foetus or neonate. Anti-Ro/SS-A, anti-La/SS-B, and to a lesser extent, anti-U1RNP autoantibodies (aAbs) have the strongest association with NLE. However, ~ 50% of affected mothers are asymptomatic despite carrying those aAbs. The clinical picture of the disease is very diverse. Cardiac manifestations are the most severe, including congenital heart block (CHB), with a mortality rate of ~18%. Preventative therapy with hydroxychloroquine (HCQ) reduces the recurrence rate of CHB in subsequent pregnancies by ~50%. [ABSTRACT FROM AUTHOR]

One of the most successful achievements of fetal intervention is the pharmacologic management of fetal arrhythmias. This management usually takes place during the second or third trimester. While most arrhythmias in the fetus are benign, both tachy‐ and bradyarrhythmias can lead to fetal hydrops or cardiac dysfunction and require treatment under certain conditions. This review will highlight precise diagnosis by fetal echocardiography and magnetocardiography, the 2 primary means of diagnosing fetuses with arrhythmia. Additionally, transient or hidden arrhythmias such as bundle branch block, QT prolongation, and torsades de pointes, which can lead to cardiomyopathy and sudden unexplained death in the fetus, may also need pharmacologic treatment. The review will address the types of drug therapies; current knowledge of drug usage, efficacy, and precautions; and the transition to neonatal treatments when indicated. Finally, we will highlight new assessments, including the role of the nurse in the care of fetal arrhythmias. The prognosis for the human fetus with arrhythmias continues to improve as we expand our ability to provide intensive care unit–like monitoring, to better understand drug treatments, to optimize subsequent pregnancy monitoring, to effectively predict timing for delivery, and to follow up these conditions into the neonatal period and into childhood. Coordinated initiatives that facilitate clinical fetal research are needed to address gaps in knowledge and to facilitate fetal drug and device development. [ABSTRACT FROM AUTHOR]

Congenital complete heart block (CCHB) is a very rare condition, with high risk of mortality. Prematurity is associated with immaturity of the cardiovascular system. Morbidity related to CCHB and prematurity has never been described. We describe a tertiary perinatal center experience over a 15-year period on CCHB management and complications in preterm infants. This is a single-center observational cohort study. All neonates admitted to neonatal intensive care unit with a diagnosis of isolated CCHB between January 2006 and January 2021 were identified. All preterm neonates (< 37 weeks) were compared with a control cohort of term neonates (≥ 37 weeks). Antenatal data, complications of prematurity, medical, and surgical management of CCHB were recorded. Twenty-four neonates with isolated CCHB (16 preterm and 8 term) were born during the study period, including 5 very preterm (< 32 weeks) and 11 preterm (32 to 37 weeks). All very preterm were born via emergency caesarian section without antenatal steroid administration. They had multiple severe morbidities including chronic lung disease, necrotizing enterocolitis, grades 3–4 intraventricular hemorrhage, cystic periventricular leukomalacia, and longer periods of mechanical and non-invasive ventilatory support than preterm. Thirteen out of sixteen preterm infants had permanent pacemakers inserted, compared to 1/8 for term newborns. All babies born before 35-week gestation were either paced or died. Conclusion: Premature neonates with CCHB have high risk of mortality and morbidity especially if undiagnosed and born by unnecessary emergency caesarian section without antenatal steroids. Prematurity below 35 weeks may be associated with death or pacemaker insertion. This supports better antenatal screening to avoid induced prematurity. What is Known: • Congenital complete heart block is a very rare condition associated with high morbidity and mortality. • Antenatal risk factors for poor outcome include fetal hydrops, low ventricular rate (HR <55 beats per minute), and congenital heart defect. What is New: • Infants born <32 weeks with CCHB had no antenatal steroid administration, and sustained high burden of morbidity (chronic lung disease, intraventricular hemorrhage, and cystic periventricular leukomalacia). • Birth <35 weeks is strongly associated with requiring pacing prior to discharge or death. [ABSTRACT FROM AUTHOR]

Sjögren's (SHOW'-grenz) syndrome is a systemic autoimmune, rheumatic disease that affects the entire body. The most common problems are dry mouth, dry eyes, fatigue and musculoskeletal pain in adults. Ten times as many women as men are diagnosed with Sjögren's. While most often diagnosed in women during middle age or after menopause. The congenital heart block (CHB) is defined as the heart block that is diagnosed in fetus (in utero) or within the first 28 days after birth (neonatal period). Congenital heart block is a rare disorder that appears to affect males and females in equal numbers. The most common cause of congenital heart block (CHB) is neonatal lupus due to maternal Sjögren's syndrome, an acquired autoimmune disease caused by transplacental transfer of maternal antibodies to the fetus. Several studies have reported an increased rate of spontaneous abortion and fetal loss associated with Sjögren syndrome. Congenital heart block occurs in a frequency of 1 in 20,000 live births. It has been reported to occur in 2% of Ro-positive mothers [2]; 5% of mothers with a diagnosis of mixed connective tissue and/or Sjögren Syndrome [3] and in 8% of Ro-positive mothers. Here we present an early pre-term neonate that was admitted to neonatal intensive care unit for bradycardia with stable haemodynamics. The mother, who showed no clinical symptoms or any particular history, was transferred to our tertiary centre for profound fetal bradycardia on recent scans. At birth, the infant's ECG showed a third-degree atrioventricular block and echocardiography was normal. Cardiac neonatal lupus was confirmed with positive maternal anti-Ro antibodies. Under close monitoring, the infant tolerated the bradycardia well (median 72 beats per minute (bpm)) and was discharged on day 21 of life. There was no indication for pacemaker at discharge, but he would be on regular follow-up with a paediatric cardiologist. [ABSTRACT FROM AUTHOR]

Congenital complete heart block (CCHB) affects 1 in 20,000 newborns. This study evaluates fetal and neonatal risk factors predictive of neonatal pacemaker placement in antibody-mediated complete heart block. The Children's Hospital Los Angeles institutional fetal, pacemaker, and medical record databases were queried for confirmed SSA/SSB cases of CCHB between January 2004 and July 2019. Cases excluded were those with a diagnosis beyond the neonatal period, diagnosis of a channelopathy, or if maternal antibody status was unknown. We recorded the gestational age (GA), birth weight (BW), fetal heart rates (FHRs) of the last echocardiogram before delivery, specific neonatal ECG and echocardiogram findings, age at pacemaker placement, and mortality. Of 43 neonates identified with CCHB, 27 had confirmed maternal antibody exposure. Variables associated with neonatal pacemaker implantation were FHRs < 50 bpm (p = 0.005), neonatal heart rates < 52 bpm (p = 0.015), and neonatal left ventricular fractional shortening (FS) percentages < 34% (p = 0.03). On multivariate analysis, FHR remained significant (p = 0.03) and demonstrated an increased risk of neonatal pacemaker placement by an odds ratio of 12.5 (95% CI 1.3–116, p = 0.05). The median GA at which the FHR was obtained was 34 weeks (IQR 26–35 weeks). Neonatal pacemaker placement was highly associated with a FHR < 50 bpm, neonatal HR < 52 bpm, and neonatal FS < 34%. FHRs at 34 weeks GA (IQR 26–35 weeks) correlated well with postnatal heart rates and were predictive of neonatal pacemaker placement. [ABSTRACT FROM AUTHOR]

Introduction: Pacing‐induced cardiomyopathy (PICM) is a potential complication of chronic right ventricular (RV) pacing, but its characterization in adult patients is often complicated by pre‐existing cardiomyopathy. This study investigated the incidence of PICM in patients with congenital heart block (cHB) who have conduction disease from birth without confounding pre‐existing cardiac conditions. Methods and Results: This retrospective cohort analysis included 42 patients with cHB and baseline left ventricular ejection fraction (LVEF) ≥50%. Kaplan–Meier analysis was used to assess freedom from cardiomyopathy (defined as LVEF <50%) between paced and nonpaced patients. Patients were 26 ± 3 years old at first presentation, 64% were women and baseline LVEF was 60.0 ± 0.2%. Median follow‐up from birth was 35 (interquartile range [IQR]: 20–42) years with a median of 6.7 years (IQR: 3.6–9.2) at our institution. Thirty‐two patients received pacing at mean age 21 ± 3 years. Patients receiving a pacemaker (PM) were significantly more likely to develop a cardiomyopathy (p =.021) and no patient developed a cardiomyopathy in the absence of a PM. Four patients who developed a new cardiomyopathy were upgraded to biventricular pacing, leading to stabilization or improvement of LVEF. Conclusion: In a relatively young and healthy cHB cohort, RV pacing is associated with a higher risk of developing a cardiomyopathy. These data confirm the deleterious effects of RV pacing on myocardial function in patients without pre‐existing structural cardiac disease and has clinical implications to the management of patients with cHB. [ABSTRACT FROM AUTHOR]

Anti-Ro antibodies are detected frequently in the general population, but more so in patients with autoimmune conditions as Sjögren’s syndrome and systemic lupus erythematous (SLE). During pregnancy, anti-Ro antibodies can cross the placenta by hijacking physiological mechanisms and can have deleterious effects on the fetus. Administration of hydroxychloroquine (HCQ) to pregnant women with documented anti-Ro antibodies has been shown to prevent congenital heart block (CHB ). Serial fetal ultrasound scans and echocardiograms are controversial in pregnant women with anti-Ro antibodies. When complete CHB is diagnosed, this is irreversible and can lead to fetal heart failure, hydrops, and death. After delivery, babies with complete CHB require pacemaker. In the presence of maternal anti-Ro antibodies, there is a high risk of recurrence of CHB for future pregnancies, if there is a previously affected child. Adequate counselling and prophylactic treatment with HCQ should be encouraged. [ABSTRACT FROM AUTHOR]

Neonatal lupus erythematosus is an autoimmune disease acquired during fetal life as a result of transplacental passage of maternal anti-Sjögren's-syndrome-related antigen A (anti-SSA/Ro), anti-Sjögren's-syndrome-related antigen B (anti-SSB/La) or anti-U1 ribonucleoprotein (anti-U1-RNP) antinuclear autoantibodies. Clinical manifestations include skin lesions, congenital heart block, hepatobiliary involvement and cytopenias. Most of the disorders disappear spontaneously after clearance of maternal antibodies. Cardiac symptoms, however, are not self-resolving and often pacemaker implantation is required. Diagnosis is based on clinical presentation and the presence of typical antibodies in the mother's or infant's serum. Neonatal lupus erythematosus may develop in children born to anti-SSA/Ro or anti-SSB/La women with various systemic connective tissue diseases. However, in half of the cases, the mother is asymptomatic, which may delay the diagnosis and have negative impact on the child's prognosis. Testing for antinuclear antibodies should be considered in every pregnant woman since early treatment with hydroxychloroquine or intravenous immunoglobulin (IVIG) has proven to be effective in preventing congenital heart block. [ABSTRACT FROM AUTHOR]

Anti-Ro/SSA antibodies are associated with a risk of 1-2 % to develop complete atrioventricular block (AVB) in fetuses of positive mothers. Complete AVB is irreversible, but studies suggest that anti-inflammatory treatment during the transition period from a normal fetal heart rate (FHR) to an AVB might stop this progression and restore sinus rhythm. The most efficient method for diagnostic evaluation of this arrhythmia is the pulsed-Doppler fetal echocardiography. However, weekly or bi-weekly recommended fetal echocardiographic surveillance can rarely identify an AVB in time for treatment success, also because the transition from a normal rhythm to a third degree AVB is very fast. Daily FHR monitoring in a medical facility could increase the chances of identifying the AVB onset but is difficult to realize. For this reason, an alternative method of FHR monitoring, performed directly by mothers in their home context, has been recently proposed. We present a case report utilizing this approach and review the current evidence about this condition. [ABSTRACT FROM AUTHOR]

An infant with congenital heart block and hemodynamically significant bradycardia underwent therapeutic temporary pacing wires placement. Post-operatively, frequent "asystole" alarms were observed on telemetry causing distress to both the family and the nursing staff. Investigation of these alarms showed that pacemaker malfunction led to monitor pseudo-malfunction. The alarms were alleviated with mindful setting of the pacemaker and telemetry monitor parameters. This case highlights the challenges of pacemaker placement and monitoring of very small infants in the intensive care setting. Awareness of these challenges would help in troubleshooting pacemaker and telemetry monitor issues. [ABSTRACT FROM AUTHOR]

Autoimmune congenital heart block (CHB) may develop in foetuses of women carrying anti‐Ro/SSA and La/SSB autoantibodies and is characterized by disruption of signal conduction at the atrioventricular (AV) node, resulting in partial or complete AV block. If not fatal in utero, complete CHB typically requires lifelong cardiac pacing. No treatment has so far been unequivocally demonstrated to prevent or treat autoimmune CHB, and the relatively low incidence (1%‐5%) and recurrence (12%‐16%) rates of second/third‐degree AV block add to the complexity of managing pregnancies in women with anti‐Ro/La antibodies. Altogether, a better understanding of events leading to development of autoimmune CHB is needed to improve surveillance and treatment strategies. In the past decade, studies have started to look beyond the role of maternal autoantibodies in disease pathogenesis to assess other contributing factors such as foetal genetics and, more recently, immune responses in foetuses and neonates of anti‐Ro/La antibody‐positive women. In this review, we provide an update on the epidemiology, clinical presentation and current treatment approaches of autoimmune CHB, summarize the previously proposed pathogenic mechanisms implicating maternal autoantibodies, and discuss the recent findings of type I interferon (IFN) and innate immune activation in foetuses with autoimmune CHB and in neonates of anti‐Ro/La antibody‐positive mothers, and how these may contribute to autoimmune CHB pathogenesis. [ABSTRACT FROM AUTHOR]

Epicardial pacing wire (EPW) insertion is an integral part of open heart surgery. However, the use of EPW insertion is also associated with complications such as bleeding, tamponade, arrhythmias, and occasionally even death of the patient. Various techniques have been described for preparing, placing, and removing EPW. We present our simple, yet effective technique of preparing, inserting, and removing EPW where the incidence of complications is nil. [ABSTRACT FROM AUTHOR]

Objectives To investigate fetal/perinatal and maternal outcomes from a large multicentre cohort of women diagnosed with UCTD. Methods This multicentre retrospective cohort study describes the outcomes of 224 pregnancies in 133 consecutive women with a diagnosis of UCTD, positive for ANA and aged <45 years old at study inclusion. Results Of the 224 pregnancies analysed, 177 (79%) resulted in live births, 45 (20.1%) in miscarriages (defined as pregnancy loss before 12 weeks' gestation), 2 (0.9%) in stillbirths (pregnancy loss after 20 weeks' gestation) and 6 (2.7%) cases showed intrauterine growth restriction. Miscarriages and stillbirths were strongly associated with the presence of aPL and ENA antibodies (P  < 0.05). Maternal pregnancy complications were as follows: 5 (2.2%) cases developed pre-eclampsia, 11 (4.9%) cases gestational hypertension and 12 (5.4%) cases gestational diabetes. Joint involvement represented the most frequent clinical manifestation of the cohort (57.9%), followed by RP (40.6%), photosensitivity (32.3%) and haematological manifestations (27.1%). The rate of disease evolution of our cohort from a diagnosis of UCTD to a diagnosis of definite CTD was 12% within a mean time of 5.3 ± 2.8 years. With a total follow-up after first pregnancy of 1417 patient-years, we observed the evolution to a defined CTD in one out of every 88 patient- years. Conclusion In our multicentre cohort, women with UCTD had a live birth rate of 79%. Women with UCTD should be referred to specialist follow-up when planning a pregnancy. ENA profiling and aPL testing should be mandatory in this setting, and further therapeutic approaches and management should be planned accordingly. [ABSTRACT FROM AUTHOR]

Background: Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB).Objectives: Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB.Methods: This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash.Results: By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4).Conclusions: These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573). [ABSTRACT FROM AUTHOR]

Aims Investigating human heart development and applying this to deviations resulting in disease is incomplete without molecular characterization of the cell types required for normal functioning. We investigated foetal human heart single-cell transcriptomes from mid-gestational healthy and anti-SSA/Ro associated congenital heart block (CHB) samples. Methods and results Three healthy foetal human hearts (19th to 22nd week of gestation) and one foetal heart affected by autoimmune-associated CHB (21st week of gestation) were subjected to enzymatic dissociation using the Langendorff preparation to obtain single-cell suspensions followed by 10× Genomics- and Illumina-based single-cell RNA-sequencing (scRNA-seq). In addition to the myocytes, fibroblasts, immune cells, and other minor cell types, previously uncharacterized diverse sub-populations of endothelial cells were identified in the human heart. Differential gene expression analysis revealed increased and heterogeneous interferon responses in varied cell types of the CHB heart compared with the healthy controls. In addition, we also identified matrisome transcripts enriched in CHB stromal cells that potentially contribute to extracellular matrix deposition and subsequent fibrosis. Conclusion These data provide an information-rich resource to further our understanding of human heart development, which, as illustrated by comparison to a heart exposed to a maternal autoimmune environment, can be leveraged to provide insight into the pathogenesis of disease. [ABSTRACT FROM AUTHOR]

Background/aim: Neonatal lupus erythematosus (NLE) is an autoimmune syndrome caused by transplacental transmission of maternal autoantibodies, often with devastating consequences. The objective of this systematic literature review was to analyze the demographic data, geoepidemiology, clinical, and serological characteristics associated with NLE. Materials and methods: We performed a systematic literature search of the Pubmed database covering the period from 1976 to August 2015, using the MeSH terms "neonatal lupus" or "congenital heart block". To be included in the study, articles of any type (original articles, case series, and case reports) had to report on infants with NLE on an individualized (i.e. patient-by-patient) basis. Results: A total of 198 studies were included in the review, reporting on a total of 755 NLE patients. The most frequently reported clinical manifestations of NLE were congenital heart block (CHB, 65.2%), cutaneous lupus (33.1%), and cytopenias (15.5%). We found differences in NLE characteristics based on study geographical origin, with CHB being much more frequent in patients of European or American descent (49.4% and 35%, respectively), while reports originating from Asia reported a higher prevalence of skin involvement (45.2%). Most CHB cases (72.9%) were diagnosed between the 18th and 26th week of gestation. Conclusions: Phenotypic differences of NLE depending on race and country may reflect true pathophysiologic differences or methodologic discrepancies. While maternal autoimmune disease is not a prerequisite for the development of NLE, the existence of a truly "immunonegative" CHB is questionable. [ABSTRACT FROM AUTHOR]

Objectives In this study we aimed to investigate foetal and maternal pregnancy outcomes from a large multicentre cohort of women diagnosed with MCTD and anti-U1RNP antibodies. Methods This multicentre retrospective cohort study describes the outcomes of 203 pregnancies in 94 consecutive women ever pregnant who fulfilled the established criteria for MCTD with confirmed U1RNP positivity. Results The foetal outcomes in 203 pregnancies were as follows: 146 (71.9%) live births, 38 (18.7%) miscarriages (first trimester pregnancy loss of <12 weeks gestation), 18 (8.9%) stillbirths (pregnancy loss after 20 weeks gestation) and 11 (5.4%) cases with intrauterine growth restriction. Maternal pregnancy outcomes were as follows: 8 (3.9%) developed pre-eclampsia, 2 (0.9%) developed eclampsia, 31 (15.3%) developed gestational hypertension and 3 (1.5%) developed gestational diabetes. Women with MCTD and aPL and pulmonary or muscular involvement had worse foetal outcomes compared with those without. Moreover, we report a case of complete congenital heart block (0.45%) and a case of cutaneous neonatal lupus, both born to a mother with positive isolated anti-U1RNP and negative anti-Ro/SSA antibodies. Conclusion In our multicentre cohort, women with MCTD had a live birth rate of 72%. While the true frequency of heart block associated with anti-U1RNP remains to be determined, this study might raise the consideration of echocardiographic surveillance in this setting. Pregnancy counselling should be considered in women with MCTD. [ABSTRACT FROM AUTHOR]

Objectives: Assuming that autoimmune congenital heart block (CHB) is a progressive disease amenable to therapeutic modulation, we introduced a surveillance program for at-risk pregnancies with the dual aim of investigating if fetal atrioventricular block (AVB) could be detected and treated before becoming complete and irreversible, and to establish the incidence of AVB I, II and III in a large prospective cohort.Methods: This was a prospective study of 212 anti-Ro52 antibody-exposed pregnancies at risk of fetal AVB that were followed weekly between 18 and 24 weeks' gestation at our tertiary fetal cardiology center from 2000 to 2015. A 12-lead electrocardiogram (ECG) was recorded within 1 week after birth. Fetal Doppler atrioventricular (AV) intervals were converted to Z-scores using reference standard values derived from normal pregnancies. Each fetus was represented by the average value of the two recordings, obtained at two consecutive visits, which resulted in the longest AV interval. AV interval values were classified into normal AV conduction (Z-score ≤ 2.0) and three levels of delayed AV conduction: Z-score > 2.0 and ≤ 3.0, Z-score > 3.0 and ≤ 4.0, and Z-score > 4.0.Results: AVB II or III developed in 6/204 (2.9%) pregnancies without a CHB history and 1/8 (12.5%) of those with a CHB history. AV intervals > 2 and ≤ 3, > 3 and ≤ 4, and > 4 were detected in 16.0%, 7.5% and 2.8% of cases, respectively, and were related to the PR interval on 185 available ECGs. Three of the five cases with AVB III and one of two cases with 2:1 AVB II developed within 1 week of AV interval Z-score of 1.0, 1.9, 2.8 and 1.9, respectively. Transplacental treatment with betamethasone was associated with restoration of 1:1 AV conduction in the two fetuses with AVB II, with a better long-term result (normal ECG vs AVB I or II) observed in the case in which treatment was started within 1 week after AVB developed. Betamethasone treatment did not reverse AVB III, although a temporary effect on AV conduction was observed in 1/5 cases. Notably, the three cases in which treatment was started within 1 week after AVB III development responded with a higher ventricular rate than the other two cases and did not require pacemaker implantation until a later age (2-5 years vs 1.5-2 months).Conclusion: Fetal AV interval is a poor predictor of CHB progression, but CHB surveillance still allows detection of fetuses with AVB II or III shortly after its development, allowing for timely treatment initiation and potentially better outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Resumen El síndrome de Sjögren primario (SSp) afecta preferentemente al sexo femenino. Los informes sobre la evolución de los embarazos en estas pacientes son pocos y contradictorios. Objetivo Describir las características del embarazo y su desenlace en mujeres con SSp, así como la morbilidad del recién nacido. Material y métodos Se incluyeron pacientes con SSp que quedaron embarazadas luego del comienzo de los síntomas de dicha enfermedad. Se describieron las características clínicas y serológicas, los factores de riesgo y las comorbilidades maternas previas. Se detalló la evolución de cada embarazo, el desenlace y las características del recién nacido. Resultados Se evaluaron 11 pacientes con 18 embarazos posteriores al inicio de síntomas: todas presentaban FAN+; 10 anti-Ro/SSA+ y 7 anti-La/SSB+. El promedio de edad en años al inicio de los síntomas fue de 24,9 (DE 6,9) y al momento del embarazo fue de 30,3 (DE 5,4). Hubo 13 embarazos previos al diagnóstico, reportándose solo un aborto espontáneo. Después de la presentación del SSp, se informaron: 2 partos prematuros, un oligoamnios, 2 roturas prematuras de membranas y 2 recién nacidos con bajo peso al nacer. Se halló un caso con bloqueo cardíaco congénito y otro con lupus cutáneo neonatal. Todas las mujeres con complicaciones obstétricas (6) presentaban Ac anti-Ro/SSA+, 5 con Ac anti-La/SSB+. Quienes no tuvieron complicaciones (5): 2 presentaban anti-Ro/SSA y anti-La/SSB+, y 2 solo anti-Ro/SSA. Conclusiones Casi la mitad de los embarazos de las pacientes con SSp analizados presentaron alguna complicación no atribuible a otro factor distinto de su enfermedad de base. Abstract Primary Sjögren's syndrome (pSS) is a condition that predominantly affects women. Reports of pregnancy outcome in these patients are limited and contradictory. Objective To describe pregnancy characteristics and outcomes and newborn morbidity in women with pSS. Material and methods We included women with pSS who became pregnant after the onset of the symptoms of the disease. Clinical and serological characteristics, risk factors and previous maternal comorbidities are described. For each pregnancy in a woman with pSS, we recorded pregnancy course and outcome and newborn condition. Results We assessed 11 patients with 18 pregnancies after the onset of pSS symptoms. All of them presented FAN +; 10 anti-Ro / SSA + and 7 anti-La / SSB +. The mean age in years at the onset of symptoms was 24.9 (SD 6.9) and at the time of pregnancy was 30.3 (SD 5.4). Thirteen pregnancies happened before the diagnosis, reporting only one miscarriage. Two preterm births, 1 case of oligohydramnios, 2 of premature membrane rupture and 2 low birthweight babies were reported after the onset of pSS symptoms. There was 1 newborn with congenital atrioventricular block and another with neonatal cutaneous lupus. All the women with pregnancy complications (n = 6) had anti-Ro/SSA antibodies. Conclusions Almost half of the pregnancies assessed in women with pSS were associated with complications not attributable to factors other than the disease. [ABSTRACT FROM AUTHOR]

Objective: Neonatal lupus erythematosus is an acquired autoimmune disease which is characterised by transplacental transition of anti- SS-A/Ro and anti-SS-B/La antibodies and binding of these antibodies to fetal tissues. Cutaneous, cardiac, hepatic and hematological manifestations can be seen. Most important and serious complication is congenital heart block and this situation is a major cause of mortality approximately in 20-30% of all patients. Effectivity of current theurepatic approaches are still a questionmark. Aim of this study is to review current literature systematically to compare different treatment options. Methods: Pubmed Medline database was literature review in August 2015. Relevant publications were seeked using the MeSH terms "neonatal lupus" and "congenital heart block"; results were restricted to studies in humans and articles in the English language. After recruiting all eligable publications, when available, treatment protocols of with congenital heart block were noted case-by-case. Results: Treatment protocols of 243 (49.3%) over 492 patients were noted. Major drug classes and their percentage of use are as follow: Steroids in 106 (43.6%) patients, intravenous immunoglobulin in 14 (5.7%) patients and hydroxychloroquine in 5 (2%) patients. 134 (55.1%) patients had no treatment. Type of steroid was known of 92 (86.7%) patients and it was dexamethasone, prednisolon and betamethasone in 54 (58.6%), 27 (29.3%), 11 (11.9%) patients, respectively. Conclusion: There is no pre-defined, accepted treatment regimen of congenital heart block. There is a large spectrum of treatment options and dosage of these options. Another question is that approxiamately half of the patients do not take any medication related to congenital heart block. Also another important point is that even prednisolon can not across the placental membrane, prednisolon was found to be used very common. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study are to determine the incidence of congenital heart block (CHB) in the Japanese population and identify maternal factors predicting fetal CHB in anti-Ro/SSA antibody positive pregnancy. Methods: A retrospective study was performed using 52,147 clinical records of pregnancies followed in a single center. For 183 anti-Ro/SSA antibody-positive women, anti-Ro52 and Ro60 antibodies were measured, and the odds of CHB in relation to maternal clinical features were calculated by multivariate analysis. The receiver-operating characteristic (ROC) curves for predicting CHB were constructed for the titers of anti-Ro/SSA, anti-Ro52 and anti-Ro60 antibodies. Results: Fetal CHB occurred in two pregnancies among those without known risks such as positive anti-Ro/SSA antibody or previous CHB-affected pregnancy, suggesting an incidence similar to that in Caucasian populations. As for the anti-Ro/SSA antibody positive pregnancies, the titers of anti-Ro/SSA, anti-Ro52 and anti-Ro60 antibodies were independent risk factors for fetal CHB and the use of corticosteroids before 18 gestational weeks was an independent protective factor. The area under the ROC was 0.84, 0.73 and 0.74 for anti-Ro52, anti-Ro60 and anti-Ro/SSA antibodies, respectively. Conclusion: CHB occurred in two among approximately 50,000 pregnancies without known risks such as positive anti-Ro/SSA antibody or previous delivery of CHB-affected babies. Measurement of anti-Ro52 antibody levels may be helpful in extracting a risk group of delivering CHB infants in the anti-Ro/SSA antibody positive pregnancy. [ABSTRACT FROM AUTHOR]

Background: Anti-p200 antibodies have been receiving growing interest in view of findings associating their presence to risk of fetal autoimmune congenital heart block (CHB). The study compares and evaluates the performance of two assays currently being used for their detection. Methods: One hundred and sixteen pregnant women positive for anti-SSA/Ro52 antibodies were considered as the study population. Fifty women negative for anti-SSA/Ro52 antibodies were considered as the control population. Anti-p200 antibodies were analyzed using two home-made ELISA assays: one with biotinylated antigen and the other with free antigen. Results: The specificity of the p200-free assay was significantly higher with respect to that of the p200-biotin assay (p=0.023). Both methods showed a high area under curve (AUC), thus, a good accuracy. There was a significant prevalence of anti-p200 antibodies when the p200-free assay was used to analyze the sera of the pregnant women with CHB fetuses (p=0.007). Cohen's κ and Spearman's ρ coefficients showed a good concordance (0.71) and a high correlation (0.93), respectively. Conclusions: The p200-free assay with respect to the biotin-based method was more specific in detecting p200 antibodies in women positive for anti-SSA/Ro52 antibodies. In addition, only the p200-free method significantly found p200 antibodies in patients with fetal CHB. [ABSTRACT FROM AUTHOR]

Background Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. Methods We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Results Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7 years [range: birth–36 years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM ( P = 0.0199; HR = 3.13 [95% CI: 1.20–8.16]), non-European origin ( P = 0.0052; HR = 4.10 [95% CI: 1.81–9.28]) and pacemaker implantation ( P = 0.0013; HR = 5.48 [95% CI: 1.94–15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n = 13, diagnosed at a median age of 0 day [birth–4 days]) and late-onset DCM (n = 22, diagnosed at a median age of 15.2 months [3.6 months–22.8 years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM ( P = 0.27; HR = 1.65 [95% CI: 0.63–4.25]). Probability of survival at 10 years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Conclusion Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB. [ABSTRACT FROM AUTHOR]

Cardiac involvement is the most severe manifestation of neonatal lupus. It is usually diagnosed as an advanced (second or third degree) atrio-ventricular (AV) congenital heart block (CHB) starting around 20 weeks of gestation. At this gestational time, a window of opportunity might exist, and fluorinated corticosteroids (FS) have been attempted as a therapeutic option. Unfortunately the quality of the studies is methodologically low, due to the retrospective design and to the rarity of autoimmune CHB. Some case reports and small case series basically suggested a possible utility of FS, mainly in the context of incomplete CHB, while larger observational retrospective studies did not find any efficacy of FS either on mortality, on the rate of pacemaker implantation, to reduce the degree of incomplete CHB or to reduce the development of cardiomyopathy. Of note the distinction between complete and incomplete AV block may be very difficult and time consuming in utero. Overall FS should not be recommended in CHB, but might be considered for a short time for a recent incomplete CHB. [ABSTRACT FROM AUTHOR]

Objectives. Congenital heart block (CHB) develops in 1-2% of anti-Ro/SSA-positive pregnancies and has a recurrence rate of 12-20%, which indicates that factors other than maternal autoantibodies are crucial for CHB to occur. Here, we aimed to evaluate the influence of factors previously associated with CHB on the occurrence of milder forms of fetal cardiac conduction disturbances, shown to occur in up to 30% of anti-Ro/SSA-positive pregnancies, and on neonatal outcome in a large cohort of prospectively followed pregnancies. Methods. The association of maternal age, season of the year and history of atrioventricular block (AVB) with the development of fetal Doppler and neonatal ECG conduction disturbances was evaluated in 212 anti-Ro52/SSA-positive singleton pregnancies. Results. Maternal age was significantly higher in AVB II-III pregnancies but was not correlated with fetal AV time intervals in fetuses without signs of AVB II-III. AV time intervals of fetuses surveilled during the winter were significantly longer than those of fetuses surveilled during the summer. Fetal AV time intervals in consecutive pregnancies from the same women were significantly correlated. A history of AVB II-III was associated with significantly longer AV time intervals, and AVB I-III was observed at birth in 38% of babies born after a sibling with abnormal fetal AV conduction. Conclusion. Our study shows that AV time intervals in anti-Ro/SSA antibody-exposed fetuses during the CHB risk period are influenced by the season of the year, and reveals that the recurrence of conduction disturbances in antibody-exposed fetuses is higher than previously reported when milder forms are taken into account. [ABSTRACT FROM AUTHOR]

While the relationship between maternal connective tissue diseases and neonatal rashes was described in the 1960s and congenital heart block in the 1970s, the “culprit” antibody reactivity to the SSA/Ro-SSB/La ribonucleoprotein complex was not identified until the 1980s. However, studies have shown that approximately 10–15% of cases of congenital heart block are not exposed to anti-SSA/Ro-SSB/La. Whether those cases represent a different disease entity or whether another antibody is associated has yet to be determined. Moreover, the cutaneous manifestations of neonatal lupus have also been identified in infants exposed only to anti-U1RNP antibodies. In this review, we describe what we believe to be the first case of congenital heart block exposed to maternal anti-U1RNP antibodies absent anti-SSA/Ro-SSB/La. The clinical and pathologic characteristics of this fetus are compared to those typically seen associated with SSA/Ro and SSB/La. Current guidelines for fetal surveillance are reviewed and the potential impact conferred by this case is evaluated. [ABSTRACT FROM AUTHOR]

Objective. Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus. Methods. Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study. A total of 315 individuals were screened and 268 participants were included. Exposure to AMs was defined as HCQ or chloroquine throughout pregnancy. Outcomes were cardiac and non-cardiac neonatal lupus. Frequentist and Bayesian analyses were performed. We hypothesized that prenatal AM exposure would decrease the risk of cardiac but not non-cardiac neonatal lupus. Results. A total of 268 pregnancies were included; 73 were exposed to AMs throughout pregnancy. Ninety-nine children developed neonatal lupus, 117 remained unaffected and 52 children did not develop cardiac neonatal lupus but could not be categorized as unaffected since their full non-cardiac neonatal lupus status was unknown. Logistic regression suggested a protective effect of AM on cardiac neonatal lupus, but results were not statistically significant [odds ratio (OR) 0.21; P = 0.07]. Bayesian analysis showed that the probability of obtaining a protective effect (OR<1.0) for cardiac neonatal lupus was significant (98.7%). The effect of AMs on non-cardiac neonatal lupus was not significant (OR 0.78; P = 0.21). Conclusion. In this large single-centre cohort study, exposure to AMs throughout pregnancy was asso- ciated with a decreased probability of developing cardiac but not non-cardiac neonatal lupus. [ABSTRACT FROM AUTHOR]

Congenital heart block (CHB) is an autoantibody mediated disorder presumably caused by placental transmission of maternal autoantibodies to Ro/SSA 52 kd, p200, Ro/SSA 60 kd, La/SSB ribonucleoproteins. This study investigated the clinical significance of isolated anti-Ro/SSA 52 kd, anti-p200, anti-Ro/SSA 60 kd, and anti-La/SSB antibodies in positive pregnant patients. One hundred sixty-three pregnant women positive to anti-Ro/SSA 52 kd and/or anti-Ro/SSA 60 kd and/or anti-La/SSB antibodies were prospectively enrolled in the study. Anti-Ro52, anti-Ro60, anti-p200, and anti-La antibodies were assayed using home-made ELISA assays. Isolated antibody positivity was found in 25 women (15.3%), while multiple antibody positivity in 138 (84.7%). Twenty-four developed CHB, and the 139 had a favorable pregnancy outcome. The prevalence of isolated anti-Ro/SSA 60 kd antibodies was significantly higher ( p < 0.046) as the prevalence of lower mean antibody titers ( p < 0.0001) in the later group. Confirmation of these results by large-scale studies could lead clinicians to recommend less stringent fetal echocardiography monitoring in women with isolated anti-Ro/SSA 60 kd antibodies. [ABSTRACT FROM AUTHOR]

Neonatal Lupus Syndrome (NLS) is a distinct clinical entity caused by transplacental passage of maternal anti -SSA/Ro antibodies (Ab). Mothers may have systemic lupus erythematosus, Sjögren syndrome, or other connective tissue disease, or may be completely healthy at the time of giving birth. NLS includes several clinical manifestations: complete congenital heart block (CCHB) and cutaneous lupus are the most common, while hepatobiliary disease, hematological manifestations and central nervous system involvement may occur. Data from literature on the incidence of the different clinical manifestations of NLS are difficult to compare because they come mostly from retrospective studies or prospective studies, but up to date no systematic follow-up was carried out. We performed a large prospective single-center study with a systematic clinical and instrumental follow-up until 9 months of life, in order to evaluate the incidence and the clinical impact of NLS features. From 2004 to 2014 all infants born in our center to mothers with anti -SSA/Ro Ab were enrolled in a specific diagnostic and follow-up (FU) program. At birth, 50 infants born to mothers with anti -SSA/Ro Ab were found positive for anti-SSA/Ro Ab. Infants were tested for anti SSA/Ro Ab at 3 months of life, if positive they were re-tested at 6 and 9 months. At 9 months anti -SSA/Ro Ab were positive in 10% of children. In two cases (4%) a CCHB was identified during pregnancy and required pacemaker implantation at birth. In 10% of cases a transient ECG alterations was found during follow-up. Hematological NLS features (anemia, neutropenia, thrombocytopenia) were found at birth and during FU in several patients, in all cases without clinical manifestations and in most cases with complete normalization at 9 months. Mild and transient elevation of aminotransferases between 3 and 6 months of life were found in 56% and 40% of patient, respectively; non-specific ultrasound cerebral anomalies in absence of clinical neurological signs were found at birth in 9 patients (18%), subsequently normalized. Prenatal maternal screening is of primary importance in order to early detect CCHB, which requires maternal treatment and pacemaker implantation at birth. Infants born to mothers with anti -SSA/Ro Ab should be monitored for all NLS features at birth. However, during the first months of life, these infants seem to develop only mild, transient and self-limited clinical manifestations, which in most cases are completely solved at 9 months of life. This consideration, together with the evidence that only 10% of infants had anti -SSA/Ro Ab persistent in blood at 9 months, suggests that follow-up of these children can be performed until 6–9 months of life with good clinical safety. Moreover, a clinical and laboratory monitoring at 3 months of life, when the highest incidence of hematological features and liver tests alterations are observed, is strongly recommended. In the future, it would be clarified if a follow-up until adulthood would be indicated in cases with persistent anti SSA/Ro or in all infants born to mother with anti SSA/Ro. [ABSTRACT FROM AUTHOR]

Congenital heart block (CHB) is a potentially lethal condition characterized by a third-degree atrioventricular block (AVB). Despite anti-Ro52 antibodies being detected in nearly 90% of mothers of affected children, CHB occurs in only 1-2% of anti-Ro/Sjögren's-syndrome-related antigen A (SSA) autoantibody-positive pregnancies. Maternal antibodies have been suggested to bind molecules crucial to fetal cardiac function; however, it remains unknown whether a single antibody profile associates with CHB or whether several specificities and cross-reactive targets exist. Here, we aimed to define further the reactivity profile of CHB-associated antibodies towards Ro52p200 (amino acid 200-239). We first analysed reactivity of a monoclonal anti-Ro52 antibody shown to induce AVB in rats (7.8C7) and of sera from anti-Ro52p200 antibody-positive mothers of children with CHB towards a panel of modified Ro52p200 peptides, and subsequently evaluated their potential to induce AVB in rats upon transfer during gestation. We observed that CHB maternal sera displayed a homogeneous reactivity profile targeting preferentially the C-terminal part of Ro52p200, in contrast to 7.8C7 that specifically bound the p200 N-terminal end. In particular, amino acid D233 appeared crucial to maternal antibody reactivity towards p200. Despite low to absent reactivity towards rat p200 and different binding profiles towards mutated rat peptides indicating recognition of different epitopes within Ro52p200, immunoglobulin (Ig)G purified from two mothers of children with CHB could induce AVB in rats. Our findings support the hypothesis that several fine antibody specificities and cross-targets may exist and contribute to CHB development in anti-Ro52 antibody-positive pregnancies. [ABSTRACT FROM AUTHOR]

Background Children from mothers with systemic lupus erythematosus are frequently born with congenital heart block. This study aimed at evaluating long-term outcome because long-term data are scarce. Methods In the database of pediatric and congenital heart disease (University Hospitals Leuven), 19 children from systemic lupus erythematosus mothers and who were born with or developed atrioventricular block were identified. All records were reviewed for disease course and outcome. Results Median follow-up time was 7 years (interquartile ranges [IQR] 4.5-13 years). One child had no heart block at birth and developed only a first-degree block during follow-up. One had a second-degree heart block and developed a complete heart block. Seventeen patients (89%) were born with a complete heart block. Seventeen patients (89%) needed a definitive pacemaker. In all, epicardial leads were used at first implantation. Eighty-two percent received their pacemaker in the first year of life. The first battery had a median lifetime of 5 years (IQR 3.5-5 years), the second 6 years (IQR 4.5-6.3 years), and the third 5 years (IQR 5-6 years). Note that 47% of patients needed a lead replacement due to lead problems. Only one pericardial tamponade after pacemaker implantation. No device or lead infections occurred. The left ventricular systolic function at latest follow-up was normal for all. No patients died. Conclusion In children with heart block born from systemic lupus erythematosus mothers, an early need for pacemaker implantation was documented. The overall battery life was acceptable, but there was a high need for lead replacement. Complication rate was low. Late outcome was good. [ABSTRACT FROM AUTHOR]

Objective: To determine the maternal predictive factors for fetal congenital heart block (CHB) in pregnancy in mothers positive for anti-SS-A antibodies. Methods: The Research Team for Surveillance of Autoantibody-Exposed Fetuses and Treatment of Neonatal Lupus Erythematosus, the Research Program of the Japan Ministry of Health, Labor and Welfare, performed a national survey on pregnancy of mothers positive for anti-SS-A antibodies. We analyzed 635 pregnant mothers who tested positive for anti-SS-A antibodies before conception but had no previous history of fetal CHB. We performed univariate and multivariate analysis (models 1, 2, and 3 using different set of independent variables) investigated the relation between risk of fetal CHB and maternal clinical features. Results: Of the 635 pregnant mothers, fetal CHB was detected in 16. Univariate analysis showed that fetal CHB associated with use of corticosteroids before conception (OR 3.72, p=0.04), and negatively with use of corticosteroids (equivalent doses of prednisolone (PSL), at -10 mg/day) after conception before 16-week gestation (OR 0.17, p=0.03). In multivariate analysis, model 1 identified the use of corticosteroids before conception (OR 4.28, p=0.04) and high titer of anti-SS-A antibodies (OR 3.58, p=0.02) as independent and significant risk factors, and model 3 identified use of corticosteroids (equivalent doses of PSL, at -10 mg/day) after conception before 16-week gestation as independent protective factor against the development of fetal CHB (OR 0.16, p=0.03). Other maternal clinical features did not influence the development of fetal CHB. Conclusion: The results identified high titers of anti-SS-A antibodies and use of corticosteroids before conception as independent risk factors, and use of corticosteroids (equivalent doses of PSL, at -10 mg/day) after conception before 16-week gestation as an independent protective factor for fetal CHB. [ABSTRACT FROM AUTHOR]

Objective Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/SSA autoantibodies, and carries substantial morbidity and mortality. The aim was to evaluate how information on CHB is imparted and identify areas of improvement. Methods A questionnaire was distributed to anti-Ro/SSA antibody-positive women who had either participated in a surveillance programme but whose expected child did not develop CHB (n = 100, denoted Doppler-Assessed Pregnancies (DAP) group) or given birth to a child with CHB (n = 88, denoted CHB-Affected Pregnancies (CAP) group). Results The response rate was 83% (157/188). Most women received the information on CHB when they were already pregnant (DAP group 60%, CAP group 83%). However, a majority of them would have wanted the information before pregnancy (DAP group 52%, CAP group 56%), and most stated that it would not have influenced their decision to have a child (DAP group 77%, CAP group 58%). The ability to both understand the information and to perceive the information as sufficient were significantly higher when someone trained in paediatric cardiology gave the information. Conclusions Our findings indicate that information on CHB should be given to women before pregnancy. The data further highlight the importance of having specific knowledge for giving relevant and understandable, yet sufficient information. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe the clinical and immunological characteristics of maternal autoimmune-mediated fetal congenital heart block (CHB) in a cohort of pregnant women from an autoimmune disease pregnancy clinic. This is a retrospective observational study of all women presenting with CHB in our autoimmune disease pregnancy clinic from January 1997 to December 2014. In addition, perinatal outcome is also described. Fourteen patients accounting for 18 fetuses with CHB were identified. The median age was 32.5 years (range, 22-40). Seven (50 %) patients had Sjögren's syndrome, and the remaining seven were asymptomatic carriers of autoantibodies. All patients had anti-Ro/SSA antibodies, and 11/13 (85 %) had anti-La/SSB antibodies. The median gestational age at the time of CHB was 22 weeks (range 18-28). Complete third degree CHB was detected in 12 (67 %). Seven cases of CHB were treated with dexamethasone, two with ritodrine, and one with the association of dexamethasone, ritodrine, and terbutaline. In 9 (50 %) cases that presented with, or developed, very poor prognosis factors, such as a ventricular rate below 50-55 bpm and/or the presence of fetal hydrops, parents opted for the termination of pregnancy, after dedicated counseling. Finally, there were nine newborns (seven males [78 %]) with median age at delivery of 37 weeks (range, 32-39). A definitive epicardial pacemaker was placed in six newborns, four of them within 2 weeks of life. CHB is a severe complication related to maternal anti-Ro/SSA and anti-La/SSB antibodies. Our results confirm previous data showing that therapy is ineffective, and most of the surviving patients will require neonatal pacemaker. [ABSTRACT FROM AUTHOR]

Autoimmune congenital heart block (ACHB) is an immune-mediated cardiac disease included among the manifestations collectively referred to as neonatal lupus. The placental transference of maternal Ro/La autoantibodies may damage the conduction tissues during fetal development leading to blocking of signal conduction at the atrioventricular (AV) node in an otherwise structurally normal heart. Irreversible complete AV block is the main cardiac manifestation of ACHB, but some babies may develop endocardial fibroelastosis, valvular insufficiency, and/or frank cardiomyopathies with significantly reduced cardiac function requiring transplant. The severity of ACHB is illustrated by a global mortality rate of 20% and pacemaker rates of at least 64%, often within the first year of life. This review analyses the main complex and/or unusual clinical situations associated with ACHB, including unusual maternal immunological profiles, infrequent maternal autoimmune diseases, cardiac damage unrelated to AV block, fetal invasive management, late complications after birth, risk of congenital heart block (CHB) in ovodonation and in vitro fertilization techniques, the role of maternal features other than autoimmunity, the influence of the birth order or the risk of CHB in twins and triplets. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the effects of maternal autoimmune disease and fetal congenital heart block (CHB) on pregnancy outcomes in anti-Ro/SSA-positive women and assessed the population-based incidence of isolated CHB.Material and Methods: One hundred and ninety nine anti-Ro/SSA-positive pregnancies were prospectively followed at our center (2000-2013). Seven fetuses developed atrioventricular block (AVB) II-III. In this period, another 13 anti-Ro/SSA-positive pregnancies were referred for fetal bradycardia, subsequently diagnosed with AVB II-III. Cesarean section rates, gestational age, body measurements at birth, and the incidence of CHB in these 212 pregnancies were analyzed in relation to fetal atrioventricular conduction and maternal diagnosis and compared with data from the Medical Birth Registry on 352,104 pregnancies in the Stockholm County.Results: The prevalence of maternal systemic lupus erythematosus (SLE) and primary Sjögren's syndrome and the outcomes at birth were similar in normal conduction and AVB I cases. Only 1/20 AVB II-III cases (0/7 in the surveillance group) had a mother diagnosed with SLE, compared with 73/192 in cases with normal conduction or AVB I. Excluding cases with AVB II-III, SLE mothers more frequently delivered by cesarean section (31% vs. 20%, p < 0.05) and had a higher incidence of preterm birth (13% vs. 5.8%, p < 0.05) than the county population. Both SLE and primary Sjögren's syndrome mothers had a fourfold greater rate of growth-retarded babies (10.11% vs. 2.2%, p < 0.001). The incidence of autoantibody-related AVB II-III in Stockholm County was 1/23 300.Conclusion: This study of CHB provides new information on the incidence of CHB and outcome of pregnancy in anti-Ro/SSA-positive women, which has clinical relevance when counseling rheumatic patients considering pregnancy. [ABSTRACT FROM AUTHOR]

Background Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB. Methods Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies. Results 214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p < 0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7–32.7]) and prematurity (p = 0.002; HR 17.1 [95%CI 2.8–103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p = 0.0157; HR 6.37 [95%CI: 1.25–32.44]), postnatal DCM (p < 0.0001; HR 227.58[95%CI: 24.33–2128.46]) and pacemaker implantation (p = 0.0035; HR 0.11[95%CI: 0.02–0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB. Conclusion In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids. [ABSTRACT FROM AUTHOR]

Objective The risk for congenital heart block (CHB) associated with maternal Ro/SSA autoantibodies is low, but the possibility of treating early stages of disease has seen the introduction of Doppler echocardiographic surveillance programs with serial examinations during the CHB susceptibility weeks of pregnancy. The aim of the present study was to understand how Ro/SSA autoantibody-positive women having undergone Doppler echocardiographic surveillance programs and giving birth to children without CHB experienced their pregnancy and frequent ultrasound examinations. Methods A validated questionnaire based on data from an interview-study was distributed to Ro/SSA-positive women supervised with Doppler examinations during their pregnancy (n = 100). Results The response rate was 79%. The majority of the women (61%) reported that the increased number of ultrasound examinations influenced their pregnancy, but in a positive way, with qualified information and additional support from health care personnel in conjunction with the examinations. Further, the visits to the clinic provided opportunities to see the ultrasound picture of the expected infant. However, one-third of the women also reported stress in relation to the examinations. Conclusions Fetal echocardiographic surveillance holds many and predominantly positive effects for Ro/SSA-positive women during pregnancy in addition to the medical advantages. [ABSTRACT FROM AUTHOR]

Aim To analyze the clinical features, outcomes and prognosis of neonatal lupus erythematosus ( NLE) in China. Method We reviewed 12 NLE cases at the Peking Union Medical College Hospital and compared the data with 111 cases reported in China between 1990 and 2014. The Chinese medical journal search engines used in this study were Wanfang.data and Science China. Results No gender dominance in NLE incidence was found. Cutaneous lesions were present in more than 96% of patients, while cardiac, hematological and hepatobiliary manifestations were seen in 12.61%, 45.53% and 17.89% of cases, respectively. Congenital heart block ( CHB) tended to be more persistent, with two cases showing CHB for 1 year and three cases persisting for 7-10 years. In this study more than 90% of mothers were anti-Sjögren's syndrome A positive, and 65.04% were asymptomatic prior to the pregnancy. Conclusion These results indicate that clinicians, especially dermatologists, in China should improve their recognition of this disease to avoid misdiagnosis, and more attention should be paid to the follow-up of NLE patients and their asymptomatic mothers. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of the combination of steroids, plasmapheresis and intravenous immunoglobulins (IVIG) on maternal anti Ro/SS-A antibody levels in cases of fetal cardiac involvement. Material and methods A series of three cases of positive anti-Ro/SS-A mothers with fetuses showing mild cardiac involvement were treated with a triple therapy composed of steroids, plasmapheresis and IVIG. Maternal antibody levels were measured several times before and after the application of each cycle of therapy. The effect of the treatment on fetal cardiac manifestations was also evaluated. Results Maternal anti-Ro/SS-A levels significantly decreased after each cycle of either plasmapheresis or IVIG therapy. The most significant decrease occurred after the first cycle. The natural evolution of the disease was stopped by this therapy in two of these cases, signs of cardiac inflammation decrease and none of the newborns needed neonatal pacemaker. Conclusions A triple therapy combining plasmapheresis, IVIG and glucocorticoids may stop the natural evolution of the fetal cardiac affectation in positive anti-Ro/SS-A antibody patients. Further studies are needed in order to validate clinical applications of this treatment approach. [ABSTRACT FROM AUTHOR]

Résumé Le lupus érythémateux néonatal se manifeste par une atteinte cutanée, hématologique, hépatique ou cardiaque incluant un éventuel bloc auriculo-ventriculaire congénital (BAVc) survenant sur un cœur indemne de cardiopathie malformative, une cardiomyopathie dilatée et une fibroélastose endocardique. Ce syndrome rare est constamment associé à la présence chez la mère d’anticorps anti-SSA/Ro et/ou anti-SSB/La. La fréquence du BAVc chez les femmes ayant une connectivite associée à un anticorps anti-SSA/Ro est estimée entre 1 et 2 %, et le risque de récurrence est évalué à environ 19 % lors d’une grossesse ultérieure. Les atteintes cutanées et systémiques sont transitoires, contrairement aux atteintes cardiaques et notamment au BAVc qui est définitif, associé à une morbidité et à une mortalité d’environ 18 %. La mise en place d’un pacemaker est nécessaire dans 2/3 des cas. Une myocardite peut être associée d’emblée ou apparaître plus tardivement. Les mères d’enfants ayant un BAVc sont le plus souvent asymptomatiques au moment de la découverte du BAVc. La physiopathologie n’est pas complètement élucidée à ce jour. Lorsqu’une femme enceinte est porteuse d’un anticorps anti-SSA/Ro, une surveillance échographique obstétricale sera réalisée tous les 15 jours entre 16 et 24 semaines d’aménorrhée et un électrocardiogramme sera fait de principe chez l’enfant. L’intérêt d’un traitement curatif in utero du BAVc par corticoïdes fluorés n’est à ce jour pas démontré. Un traitement préventif par hydroxychloroquine semble diminuer le risque de récidive du BAVc chez les femmes ayant déjà eu un enfant atteint. Une étude prospective est en cours pour confirmer ces résultats. Neonatal lupus syndrome is associated with transplacental passage of maternal anti-SSA/Ro and anti-SSB/La antibodies. Children display cutaneous, hematological, liver or cardiac features. Cardiac manifestations include congenital heart block (CHB); endocardial fibroelastosis and dilated cardiomyopathy. The prevalence of CHB in newborns of anti-Ro/SSA positive women with known connective tissue disease is between 1 and 2% and the risk of recurrence is around 19%. Skin and systemic lesions are transient, whereas CHB is definitive and associated with significant morbidity and a mortality of 18%. A pacemaker must be implanted in 2/3 of cases. Myocarditis may be associated or appear secondly. Mothers of children with CHB are usually asymptomatic or display Sjogren's syndrome or undifferentiated connective tissue disease. In anti-Ro/SSA positive pregnant women, fetal echocardiography should be performed at least every 2 weeks from the 16th to 24th week gestation. An electrocardiogram should be performed for all newborn babies. The benefit of fluorinated corticosteroid therapy for CHB detected in utero remains unclear. Maternal use of hydroxychloroquine may be associated with a decreased recurrent CHB risk in a subsequent offspring. A prospective study is actually ongoing to confirm these findings. [ABSTRACT FROM AUTHOR]