RESUMEN
BACKGROUND: The risk of fetal atrioventricular block in anti-Ro/SSA antibody-exposed pregnancies with no previous affected offspring is approximately 2%. A high antibody titer is necessary but not sufficient for atrioventricular block, and specific antibody titers do not predict risk. However, there are no data on the negative predictive value of antibody titer to identify pregnancies at low risk of fetal atrioventricular block, and may not require surveillance. OBJECTIVE: This study aimed to define anti-Ro52 and anti-Ro60 antibody thresholds for the identification of fetuses unlikely to develop atrioventricular block using clinically validated and research laboratory tests. STUDY DESIGN: This study performed a multicenter review of pregnant subjects who tested positive in their local commercial laboratories for anti-Ro/SSA antibodies at the University of Colorado Children's Hospital (2014-2021) and Phoenix Children's Hospital (2014-2021) and enrolled in the Research Registry for Neonatal Lupus (RRNL) at New York University Langone Medical Center (2002-2021). The subjects were referred on the basis of rheumatologic symptoms or history of atrioventricular block in a previous pregnancy and were retrospectively grouped on the basis of pregnancy outcome. Group 1 indicated no fetal atrioventricular block in current or past pregnancies; group 2 indicated fetal atrioventricular block in the current pregnancy; and group 3 indicated normal current pregnancy but with fetal atrioventricular block in a previous pregnancy. Maternal sera were analyzed for anti-Ro52 and anti-Ro60 antibodies using a clinically validated multiplex bead assay (Associated Regional and University Pathologists Laboratories, Salt Lake City, UT) and a research enzyme-linked immunosorbent immunoassay (New York University). This study calculated the negative predictive value separately for anti-Ro52 and anti-Ro60 antibodies and for the 2 combined using a logistic regression model and a parallel testing strategy. RESULTS: This study recruited 270 subjects (141 in group 1, 66 in group 2, and 63 in group 3). Of note, 89 subjects in group 1 had data on hydroxychloroquine treatment: anti-Ro/SSA antibody titers were no different between those treated (n=46) and untreated (n=43). Mean anti-Ro52 and anti-Ro60 titers were the lowest in group 1 and not different between groups 2 and 3. No case of fetal atrioventricular block developed among subjects with anti-Ro52 and anti-Ro60 titers of <110 arbitrary units per milliliter using the multiplex bead assay of the Associated Regional and University Pathologists Laboratories (n=141). No case of fetal atrioventricular block developed among subjects with research laboratory anti-Ro52 titers of <650 and anti-Ro60 of <4060 enzyme-linked immunosorbent immunoassay units (n=94). Using these 100% negative predictive value thresholds, more than 50% of the anti-Ro/SSA antibody pregnancies that ultimately had no fetal atrioventricular block could be excluded from surveillance based on clinical and research titers, respectively. CONCLUSION: Study data suggested that there is a clinical immunoassay level of maternal anti-Ro/SSA antibodies below which the pregnancy is at low risk of fetal atrioventricular block. This study speculated that prospectively applying these data may avert the costly serial echocardiograms currently recommended for all anti-Ro/SSA-antibody positive pregnancies and guide future management.
RESUMEN
Introducción: la electrocardiografía fetal constituye la prueba de oro para el diagnóstico de las arritmias en la vida posnatal, algo difícil de lograr en la vida prenatal incluso con la ecografía prenatal de alta resolución. Las taquiarritmias supraventriculares son las que se manifiestan con frecuencias cardíacas superiores a 180 latidos por min y pueden asociarse a mortalidad fetal en un tercio de los casos, sobre todo cuando se asocia a hidropesía fetal o cuando se establece por más de 15 días. El tratamiento permite la reversión de la arritmia o el control ventricular en el menor tiempo posible. Objetivos: comprobar la respuesta intraútero de la taquiarritmia al tratamiento farmacológico. Métodos: se realizó un estudio descriptivo prospectivo observacional de un universo de 24 fetos con el diagnóstico de taquiarritmia fetal que se diagnosticaron y atendieron en el Departamento Provincial de Genética de La Habana y en el Hospital Ginecobstétrico "Ramón González Coro" entre los años 2003 y 2012. Resultados: las taquiarritmias se observaron en 24 fetos (40,6 %). Las madres menores 30 años fueron las más representadas en el grupo de mujeres del estudio, unido al índice de masa corporal sobrepeso y específicamente las pacientes nulíparas. Casi la mitad de la muestra no requirió tratamiento farmacológico (45,8 %) todas con el diagnóstico ecocardiográfico de extrasístoles y sola una con compromiso orgánico del corazón. Conclusiones: la flecainida se utilizó, en la cuarta parte de la muestra y mostró una resolutividad de 83,3 % en los fetos intraútero. La sobrevida de los fetos tratados farmacológicamente por vía oral fue 100 %.
Introduction: fetal electrocardiography is the gold standard for diagnosis of arrhythmias in postnatal life. This is difficult to achieve in prenatal life even with high-resolution prenatal ultrasound. Supraventricular tachyarrhythmias are manifested with heart rates above 180 beats per min and may be associated with fetal death in one third of cases, especially when associated with fetal hydrops or when it is set for over 15 days. Treatment allows the reversal of ventricular arrhythmia or control in the shortest possible time. Objective: to test tachyarrhythmia in uterus response to drug treatment. Methods: an observational prospective descriptive study was conducted in a universe of 24 fetuses with the diagnosis of fetal tachyarrhythmia that were diagnosed and treated at the Provincial Department of Genetics, Havana and at the Ramón González Coro Maternal Hospital from 2003 to 2012. Results: tachyarrhythmias were observed in 24 fetuses (40.6 %). Mothers younger than 30 were the most represented in this study group, together with BMI overweight and nulliparous patients specifically. Almost half of the sample did not require drug (45.8 %) treatment, all with extrasystoles echocardiographic diagnosis and only one with organic heart involvement. Conclusions: flecainide was used in a quarter of the sample and showed 83.3 % resoluteness of fetuses in uterus. Survival of fetuses pharmacologically orally treated was 100 %.
RESUMEN
Congenital heart block is a fetal arrhythmia detected by routine prenatal ultrasound. Natural history and risk factors for this condition are known. Patients having Ro/La antibodies have 2 to 4 percent risk of affected child and recurrence of up to 25 percent. There are standarized protocols for measuring the PR interval by ultrasound, as well as reference curves for different gestational ages. The experience at Hospital Clínico de la Universidad Católica de Chile is reported, describing follow up of 37 patients over a period of more than 4 years. A protocol based on monthly monitoring of risk group was adopted.
El bloqueo aurículo ventricular congénito constituye una de las arritmias fetales detectables mediante ultrasonido prenatal de rutina. Se conoce su evolución natural y la población de riesgo de sufrir esta afección. En portadoras de anticuerpos Ro/La el riesgo de un hijo afectado es entre 2 y 4 por ciento, y la recurrencia de hasta un 25 por ciento. Existen protocolos estandarizados para medir el intervalo PR mediante ultrasonido, como también curvas de referencia para las distintas edades gestacionales. Reportamos la experiencia en el Hospital Clínico de la Universidad Católica de Chile, con un seguimiento de 37 pacientes en un periodo de más de 4 años. Se adoptó un protocolo de seguimiento mensual del grupo de riesgo.