Associations of Nonspecific Autoantibodies with Recurrent Pregnancy Loss and Pregnancy Outcomes Following Immunological Intervention: A Single-Centre Retrospective Cohort Study.

Abstract

Background: Immune dysfunction has been implicated in the aetiology of recurrent pregnancy loss (RPL). While there are currently clear guidelines for the diagnosis and treatment of connective tissue diseases and typical/atypical antiphospholipid syndrome, with highly effective outcomes, none exist for patients with RPL who, despite a lack of clinical symptoms, have abnormal levels of two or more immune-related markers. This study aimed to evaluate the relationship between non-specific autoantibodies and RPL, as well as the impact of immunotherapy on pregnancy outcomes in patients with RPL and positive antinuclear antibody (ANA) profiles.

Methods: A comparison was made between the prevalence of ANAs in patients with recurrent spontaneous abortion (RPL) and that in women with normal pregnancies. Additionally, the pregnancy outcomes of 102 pregnant women-who were found to be positive for a profile of two or more ANAs during follow-up at our hospital's rheumatology and immunology outpatient clinic and reproductive medicine department-were assessed following early immunomodulatory treatment [hydroxychloroquine (HCQ, 0.2 g per dose, twice daily) + glucocorticoids (prednisone 5-10 mg/day) + aspirin 0.1 g/day]. We then compared these outcomes with those of ANA-positive pregnant women attending the Reproductive Medicine Department who did not receive immunotherapy.

Results: In the observation group of 102 cases, 76 women gave birth successfully following early immunological intervention, with a normal pregnancy rate of 76/87 (87.4%). In the control group of 90 cases, the normal pregnancy rate was 27/64 (42.2%). A comparison of the sustained pregnancy rates between the two groups revealed a statistically significant difference (χ² = 34.69, P < 0.001). A higher proportion of women with abnormal ANA levels were observed in the group with normal pregnancies. Among women with recurrent pregnancy loss (RPL) and abnormal ANA levels, the higher the ANA positivity rate, the higher the miscarriage rate; women with RPL and abnormal ANA levels achieved a significantly higher pregnancy success rate following immunotherapy than those who did not receive immunotherapy.

Conclusion: In patients with recurrent pregnancy loss who exhibit autoimmune features, higher ANA titres, a greater number of positive ANA specificities, elevated IgG levels, and decreased complement levels are each independently associated with an increased likelihood of recurrent miscarriage. Importantly, early immunomodulatory intervention appears to mitigate these adverse pregnancy outcomes.