Antinuclear antibodies positivity is a risk factor of recurrent pregnancy loss: A meta-analysis

Immunologic mechanisms have been proposed as part of the pathogenesis mechanisms involved in recurrent pregnancy loss (RPL). Presence of positive antinuclear antibodies (ANA) is regarded as a typical feature of autoimmunity. Many studies had tried to clarify the association of ANA with RPL, but the conclusions were controversial. The aim of this meta-analysis was to assess whether ANA was positively associated with increased RPL risk. We searched PubMed and Embase databases for relevant literatures on the association between ANA positivity and RPL. The odds ratios (OR) with 95% confidence intervals (95%CI) were pooled using meta-analysis, and either fixed-effect or random-effect model was used based on heterogeneity across the included studies. Twenty-one studies with 5038 participants (including 2683 RPL patients and 2355 controls) met the inclusion criteria were included. The total positive rate of ANA was 22.0% (591/2683) in RPL group, and 8.3% (196/2355) in the control group. RPL patients had a significantly higher ANA positive rate than controls (OR = 2.97, 95%CI 1.91-4.64, P<0.00001; I² = 75%), and a significant association between positive ANA and unexplained RPL was also observed (OR = 3.27, 95%CI 2.01-5.31, P<0.00001; I² = 70%). ANA positivity was also significantly associated with increased risk of RPL in women without defined autoimmune diseases (OR = 2.23, 95%CI 1.40-3.55, P=0.0007). Subgroup analysis demonstrated low titers of ANA (1:40≤ANA≤1: 80) were not associated with RPL (OR = 2.44, 95%CI 0.42-14.06, P=0.32), while higher ANA titer (≥1:160) had a significant association with RPL (OR = 45.89, 95%CI 8.44-249.45, P<0.00001). A higher rate of homogenous pattern in RPL patients was observed (OR = 4.89, 95%CI 2.20-10.87, P<0.001), and no significant difference in speckled pattern or nucleolar pattern was found. This study demonstrated that ANA positivity was positively associated with increased RPL risk. ANA positivity is an important risk factor for RPL which needed to be screened among women with RPL.