Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies

Abstract

Objective: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB).

Methods: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB.

Results: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal.

Conclusion: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.

Figure 1.

Enrollment and surveillance of anti-SSA/Ro+ mothers. There were 413 pregnant patients prospectively enrolled in the STOP BLOQ study. Anti-SSA/Ro autoantibody testing identified 152 patients as Group 1 subjects who underwent weekly, biweekly, other (once at 17 and 20 weeks), or no fetal echocardiograms per standard of care. Anti-SSA/Ro autoantibody testing identified 261 patients as Group 2 performing FHRM surveillance and weekly or biweekly echocardiograms until 26 weeks. Surveillance detected AVB in 10 subjects, all Group 2. *Two patients were included in Group 2 because of a previous child with AVB. Despite having titers below the threshold, these patients were considered to be at AVB risk and underwent the surveillance protocol. **Twenty-one patients in Group 2 monitored for less than a week but did complete the echocardiograms. None of these subjects had AVB.

Figure 2.

The distribution of study-wide levels of anti-Ro52 titers (left) and anti-Ro60 titers (right) in participants. Shown on the y-axis are titers as ELISA units (EU)/mL with each dot representing 1 subject. Pink, yellow, green and white circles represent the distribution of the 4 groups of anti-Ro titers as indicated by the insert. The lower and upper dashed lines indicate 1000 EU/mL and the threshold above the third quartile, respectively. For anti-52kD SSA/Ro the upper third quartile was 20,012; for anti-60kD SSA/Ro, it was 19,744. The 10 subjects with AVB are depicted as black dots, all of whom are above the 1000 EU/threshold for both anti-Ro60 and anti-Ro52.

Figure 3:

Anti-52kD and 60kD SSA/Ro antibodies in pregnancies affected and unaffected by AVB in the same subject. A) Anti-Ro 52 titers and B) Anti-Ro 60 titers assessed by ELISA in the sera from 15 mothers during matched AVB and healthy pregnancies. Each color denotes the same mother for anti-52kD SSA/Ro and anti-60kD SSA/Ro. Open circles: an AVB pregnancy not exposed to hydroxychloroquine (HCQ); closed circles: an AVB pregnancy exposed to HCQ; open squares: a healthy pregnancy not exposed to HCQ; closed squares: a healthy pregnancy exposed to HCQ. Dotted lines represent quartiles calculated from Group 2 patients.