Maternal systemic lupus erythematosus and the risk of congenital cardiovascular abnormalities in offspring: a systematic review and meta-analysis.

Authors

Kuaifa Fang, Lifu Tan, Lianyue Wu

Published in

Immunologic research. Volume 74. Issue 1. Sep 09, 2026. Epub Sep 09, 2026.

Abstract

Maternal systemic lupus erythematosus (SLE) has been associated with adverse fetal outcomes; however, the risk of structural cardiovascular malformations and congenital heart block (CHB) remains incompletely characterized. This systematic review and meta-analysis quantified the incidence of these two distinct outcomes in offspring of mothers with SLE and explored possible correlates. Electronic databases were searched through January 2026. The pooled prevalence was estimated using random-effects models with the Freeman-Tukey double arcsine transformation. Pooled odds ratios (ORs) were calculated for comparative analyses. Exploratory meta-regression and prespecified subgroup analyses were performed to explore sources of heterogeneity. Multivariable-adjusted estimates were synthesized when available. Fifty-three studies comprising 33,694 SLE-associated pregnancies were included. The pooled incidence was 3.29% (95% CI: 2.48-4.21%) for structural cardiovascular malformations (41 studies, 32,133 pregnancies) and 1.29% (95% CI: 0.82-1.88%) for CHB (45 studies, 28,117 pregnancies). In exploratory study-level meta-regression, active disease rate was positively associated with structural malformations (P = 0.024). For CHB, subgroup analysis showed higher prevalence in studies in which CHB cases occurred in anti-SSA/Ro-positive mothers (2.64%) than in studies not reporting antibody status (0.63%; P-interaction < 0.001). Compared with healthy controls, offspring of mothers with SLE had a significantly increased risk of structural malformations (OR 3.52, 95% CI: 2.13-5.81; P < 0.001), which persisted in a pooled analysis of five multivariable-adjusted studies (OR 1.70, 95% CI: 1.22-2.36; P = 0.002), although confounder adjustment was heterogeneous and incomplete across studies. For CHB, the comparative risk estimate was elevated but highly imprecise and statistically unstable. Maternal SLE is associated with an increased risk of structural cardiovascular malformations in offspring, whereas evidence for CHB is less robust and limited by rare-event instability and antibody-status heterogeneity. The independent contribution of SLE itself remains uncertain because of incomplete adjustment for antibody status, disease activity, medication exposure, and surveillance intensity. Future prospective studies with rigorous confounder adjustment are warranted to clarify the independent effect of SLE itself.

PMID:
42714705
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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