Is stillbirth a risk factor for development of systemic lupus erythematosus in the UK?

Is stillbirth a risk factor for development of systemic lupus erythematosus in the UK?

H Kither, A Heazell, I Crocker, C Tower

Maternal & Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

Introduction
Autoimmune Connective Tissue Diseases (CTDs), such as Systemic Lupus Erythematosus (SLE), have a female preponderance and are associated with an adverse pregnancy outcome (APO). This study assessed the prevalence of CTDs, antiphospholipid syndrome (APS) and autoimmune antiphospholipid antibodies (aPL), in women with an APO, compared to those who had an uncomplicated livebirth.

Methods
A national study was performed, using the Clinical Practice Research Datalink (CPRD) for the timeframe 01/01/2000-31/12/2013. Each case of APO was matched to 5 livebirths by primary care practice and maternal age. Women were followed serially for SLE diagnosis, CTD, APS or autoimmune antibodies. Poisson regression was performed to calculate relative risk ratios (RR) and 95% confidence intervals (CI) for the development of these conditions for APO vs. livebirth.

Results
CPRD identified 20,123 APOs, matched to 97,323 livebirths. 875,590 person-years follow-up was available. Mean follow-up was 7.45 years (SD 4.39). 1,850 new autoimmune diagnoses were recorded, with an SLE incidence of 0.05%. Stillbirth was associated with an increased risk of developing specific autoimmune conditions (RR 5.82 (95% CI 4.97-6.81)), as was miscarriage (RR 3.41 (95% CI 3.03-3.85)), fetal growth restriction (RR 2.69 (95% CI 1.50-4.83)) and placental abruption (RR 3.39 (95% CI 1.96-5.89)). For SLE specifically, the risk was greatest following stillbirth (RR 4.10 (95% CI 3.14-5.36)). For CTD, SLE and development of non-aPL antibodies, the risk was greatest within 4 years of APO, whereas aPL antibody and APS diagnosis were highest ≥ 5 years from APO.

Conclusions
APO is associated with an increased risk of subsequent development of maternal CTD, including SLE. This may result from an underlying immunological factor which predisposes women to both APO and subsequently CTD development or that APO initiates an autoimmune process which culminates in the development of clinically evident CTD.

Ethics statement
Ethical approval was granted by the Independent Scientific Advisory Committee (ISAC) (protocol 14_106R).

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