Association between Serum TNF-[alpha] Levels and Recurrent Spontaneous Miscarriage: A Meta-analysis

Most recurrent spontaneous miscarriages (RSMs) are attributed to 'unexplained' factors, the majority of which are immune factors. Furthermore, clinically, only a small number of RSM patients get early diagnosis by testing for antiphospholipid antibodies, whereas most of the patients, present no specific diagnostic indicators. We performed a meta-analysis of observational studies to detect the association between RSM and TNF-[alpha] levels. We searched PubMed, EMBase, ScienceDirect, Web of Science, and Chinese databases (including: Wanfang Data, CNKI, and VIP databases) for articles published up to 2014. Of the 151 initially identified studies, 11 case-control studies with 1371 patients were finally analyzed. Overall, baseline TNF-[alpha] levels were higher in patients than in controls. The standardized mean difference of the TNF-[alpha] levels of the patients was 2.82 units (95% confidence interval 1.57-4.06) and the overall effect z-score was 4.42 (P < 0.0001). The heterogeneity test revealed significant differences among individual studies (P = 0.000, I2 = 98.7%). Serum TNF-[alpha] levels were significantly increased in patients relative to those in controls. The heterogeneity could be attributed to the differences in the detection methods and sampling times used in the different studies.