Antinuclear Antibody Positivity As a Risk Factor for Recurrent Pregnancy Loss: A Meta-Analysis

Background: Immunologic mechanisms have been one of the suggested causes of recurrent pregnancy loss (RPL). Antinuclear antibody positivity has been regarded as a typical feature of autoimmunity. Over past years many studies tried to clarify the association of ANA with RPL and the conclusions are controversial. The aim of this meta-analysis was to assess whether the presence of ANA directly increase the risk of RPL in women who did not have definite autoimmune diseases. Methods: We searched PubMed and Embase databases for relevant literatures, which included the data of ANA rate in RPL and control groups. Both fixed-effects and randomized-effects model were used to analyze the risk odds ratio with 95% confidence intervals (CIs) according to the heterogeneity across the selected studies. Findings: Twenty-one studies with 5038 participants including 2683 patients with RPL met the inclusion and exclusion criteria. The total positive rate of ANA was 22·4% (601/2683) in total RPL patients and 20·2% (397/1959) in unexplained RPL patients, respectively. Patients with total RPL or unexplained RPL had a significantly higher ANA positive rate than control groups [(OR =3·12, 95% CI:1·96, 4·97, I² = 77%), (OR = 3·47, 95% CI: 2·07, 5·81), I² = 74%], respectively]. Subgroup analysis demonstrated low titers of antibody (≤1: 80) were not associated with RPL patients [OR = 1·22, 95% CI (0·79, 1·90), I2 =86·1%], while higher ANA titer (≥1:160) showed a significant association between ANA and RPL patients [OR = 23·23, 95% CI (4·18,129·25, I 2 =0%)]. Higher rate of homogenous pattern in RPL group was observed [OR = 4·54, 95% CI (2·01, 10·24), I2=0%], and no significant difference in speckled pattern [OR = 1·08, 95% CI (0·69, 1·70), I 2 =0%] nor nucleolar pattern [OR = 3·52, 95% CI (0·93, 13·30), I 2 =0%] was found. Three studies detected the anti-dsDNA in two groups and the results demonstrated no significant difference between RPL group and controls [OR = 1·35, 95% CI (0·52, 3·54), I2=0%]. Interpretation: This is the first meta-analysis about the association between ANA positivity and RPL. The pooled data demonstrated increased prevalence of ANA in patients with RPL. ANA is suggested as a risk factor for RPL and should be recommended for this population. Funding Statement: The work was supported by Natural Science Foundation of China (NSFC) Grant U1605223 to Dr. Guixiu Shi, NSFC grant 81501407 to Dr. Yuan Liu; NSFC grant 81501369 to Dr. Shiju Chen; and the Leadership Program of the Technology Department of Fujian Province (Grant NO. 2015D011) to Dr. Guixiu Shi. Declaration of Interests: The authors declare no conflicts of interests. Ethics Approval Statement: The meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.