Objective To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion(RSA).Methods A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital.Women with RSA were recruited and multiple autoantibodies were tested.Multivariate logistic regression was performed to compare the associations between different age groups(20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group)and multiple autoantibodies,while controlling for three confounding factors,including body mass index(BMI),previous history of live birth,and the number of spontaneous abortions.Then,we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women.Result A total of 4 009 women with RSA were covered in the study.Among them,1 158 women were in the advanced maternal-age group and 2 851 women were in the low maternal-age group.The prevalence of antiphospholipid syndrome,systemic lupus erythematosus,Sjogren's syndrome,rheumatoid arthritis,and undifferentiated connective tissue disease was 15.6% and 14.1%,0.0% and 0.1%,0.9% and 0.9%,0.3% and 0.0%,and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group,respectively,showing no statistical difference between the two groups.The positive rates of antiphospholipid antibodies(aPLs),antinuclear antibody(ANA),extractable nuclear antigen(ENA)antibody,anti-double stranded DNA(dsDNA)antibody,anti single-stranded DNA(ssDAN)antibody,antibodies against alpha-fodrin(AAA),and thyroid autoimmunity(TAI)were 19.1% and 19.5%,6.6% and 6.6%,9.2% and 10.5%,2.0% and 2.0%,2.2% and 1.2%,5.1% and 4.9%,and 17.8% and 16.8%,respectively.No differences were observed between the two groups.1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant(LA),while 2.7% of the women in the low maternal-age group were LA positive,with the differences being statistically significant(odds ratio=0.36,95% confidence interval:0.17-0.78).In the 4 008 RSA patients,the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778,of which 520 cases were positive for anti-β2 glycoprotein Ⅰ antibodies(β2GPⅠ Ab)-IgG/IgM,58 were positive for aCL-IgG/IgM,73 were positive for LA,105 were positive for both β2GPⅠAb-IgG/IgM and aCL-IgG/IgM,17 were positive for both β2GPⅠ Ab-IgG/IgM and LA,2 were positive for both aCL-IgG/IgM and LA,and 3 were positive for all three antibodies.Conclusion Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.