Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that primarily affects women during the childbearing years. Among its protean manifestation, pregnancy complications including premature delivery and preeclampsia are common. Most studies of pregnancy outcomes in women with SLE focus on complications occurring in the second half of pregnancy rather than evaluating spontaneous abortions (Sab, or miscarriage) that generally occur before 14 weeks of gestational age. While Sab occurs in up to 20% of all pregnancies and sporadic Sab is often attributed to karyotypic or genetic anomalies, it is possible that women with SLE experience higher rates of Sab than healthy women, and this may have an immunologic basis. The presence of the antiphospholipid antibody syndrome is the most commonly recognized risk factor for pregnancy morbidity; as late pregnancy morbidity or >3 consecutive Sab itself meets criteria for the syndrome. We sought to understand the incidence of Sab in a large cohort of SLE women, their unaffected sisters, and unrelated unaffected women.

Methods: Clinical data and stored sera from the Lupus Family Registry and Repository of 1608 parous women between ages 20-45 including SLE patients (by ACR criteria, n=832), sisters of SLE patients (n=337), and unaffected, unrelated women (n=439) were utilized. Complete reproductive history, including gestational age and outcome of all pregnancies, was available as was standardized SLE serologies. Additional autoantibodies, related to exposure to paternal antigens, included antibodies against HLA class I and II, and antibodies directed at minor histocompatibility antigens on the Y-chromosome and their X-homologues were assessed. Ratios of the number of Sab to the total numbers of pregnancies were compared between the three groups. Regression models were developed to better understand the role of auto-or allo-immunization and risk of Sab. Analyses were repeated using the subset of 1050 women who were APL negative.

Results: Both women with SLE and their unaffected sisters had higher Sab to total pregnancy ratios than healthy women in a dose-dependent fashion: Odds Ratio (OR)=1.43 (p=0.000049) for SLE and OR=1.28, (p=0.019) for sisters. Preliminary multivariate regression analyses found that only group and +APL antibodies were significantly associated with increased Sab, neither other standard SLE antibodies nor antibodies against HLA, HY, or HX were significant.

When women with +APL were removed from the analyses the Sab ratio remained significantly different for SLE (OR=1.37, p=0.0156), but not for sisters (OR=1.11, p=0.4029) compared to healthy women. Prevalence of autoantibodies did not modify the result in multivariate models.

Conclusion: SLE women have higher rates of Sab than healthy women, and sisters of SLE patients have intermediate rates. Autoantibodies do no explain these differences.

Table

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/lupus-patients-and-their-sisters-have-higher-miscarriage-rates-than-healthy-women/