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.
Key words
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Article Info
Publication History
Published online: June 08, 2022
Accepted:
May 31,
2022
Received in revised form:
May 24,
2022
Received:
March 1,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
J.P.B. and B.F.C. contributed equally to this work as senior authors.
The authors report no conflict of interest.
This work was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development , United States (grant number R01 HD100929 [J.P.B. and B.F.C]), National Institute of Arthritis and Musculoskeletal and Skin Diseases , United States (grant numbers R37 AR042455 and N01 AR42271 [J.P.B.]), and National Heart, Lung, and Blood Institute , United States (K01 grant number HL151754 [A.M.K.]). The Associated Regional and University Pathologists Laboratories provided a grant to perform the anti-Ro/SSA antibody assays from New York University subjects. The funding sources were not involved in the study design, data collection, data analysis and interpretation, manuscript preparation, or manuscript submission.
Cite this article as: Kaizer AM, Lindblade C, Clancy R, et al. Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers. Am J Obstet Gynecol 2022;XX:x.ex–x.ex.
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