Benefits of fetal echocardiographic surveillance in pregnancies at risk of congenital heart block: single‐center study of 212 anti‐Ro52‐positive pregnancies

Abstract

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.

Treatment and follow-up of fetuses that developed congenital heart block due to autoantibody in two cases

“…11 Furthermore, this degree of block can stabilize third-degree AV block, increase the ventricular rate, improve cardiac function, and prevent complications, such as cardiomyopathy or fetal edema. According to a study by Sonesson et al, 12 even if the clinical significance of fetal AV conduction delays remains to be determined, a fetal AV interval of >150 to 155 ms may be a marker of permanent disruption of AV conduction pathways, especially when observed in two consecutive examinations. Although ACHB may be detected as early as the middle stage of pregnancy, there is still no uniform clinical guideline for reference in terms of prenatal intervention and postnatal treatment.…”

Geoepidemiology and clinical characteristics of neonatal lupus erythematosus: a systematic literature review of individual patients’ data

“…Anti SS-A/Ro (60 kDa Ro, 52 kDa Ro or calreticulin) and anti SS-B/La are responsible for direct toxic effects on the myocardium and other organs, when transferred from mother to fetus [3,4]. The risk for congenital heart block (CHB) is ~ 1%-2%, in cases of maternal positivity for anti SS-A/Ro and/or anti SS-B/La antibody, but rises to almost 18% in cases with a history of CHB in a prior pregnancy (Brito-Zeron, Izmirly, Ramos-Casals, Buyon, & Khamashta, 2015) [5]. The presence of anti SS-A/Ro and anti SS-B/La antibodies is necessary but not sufficient to cause CHB and the complete NLE syndrome, as environmental and foetal factors seem to play an additional role [6][7][8].…”

Keeping upbeat to prevent the heartbreak of anti‐Ro/SSA pregnancy

“…We now appreciate that the phenotype of cardiac NL is variable, ranging from clinically silent AVB I that does not progress, to AVB III with cardiomyopathy that progresses to hydrops and fetal demise in < 1 week 8 . Lastly, we know that the fetal AV and the neonatal PR intervals are mutable, and that an AV interval considered to indicate AVB I may not progress to AVB II or AVB III, even in the absence of treatment [6][7][8][9][10][11][12][13][14][15][16][17][18][19] . This raises the possibility that a prolonged AV interval in humans may represent a distinct anti-Ro/SSA pathologic process, or there may be an unidentified protective genetic or environmental factor in some cases, which keeps injury in check.…”

“…Because robust evidence‐based guidelines are not available, there is no agreement regarding the best type or frequency of surveillance, and further studies are needed to guide management of these pregnancies. The study of Sonesson et al ,. in this issue of the Journal, summarizes prospective data from a single center in which 212 anti‐Ro52/SSA‐positive pregnancies in 155 mothers underwent surveillance by weekly fetal echocardiography (when possible) between 18 and 24 weeks of gestation.…”