Association between Serum TNF-α Levels and Recurrent Spontaneous Miscarriage: A Meta-analysis

Abstract

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-α 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-α levels were higher in patients than in controls. The standardized mean difference of the TNF-α 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, I(2) = 98.7%). Serum TNF-α 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.

Disturbed inflammatory/anti-inflammatory milieu and activation of Primary Phase Reactants may underlie Development and Recurrence of First trimester Pregnancy Loss.

“…Also, Ozkan et al (18) detected a significantly high TNF-a/IL-10, TNF-a/ IL-4 and concluded that increased Thl /Th2 cytokine ratios in RPL cases pointed to suppression of antiinflammatory process that might play an important role in the pathogenesis of idiopathic RPL. Recently, Zhang et al (19) found baseline TNF-a levels were higher in patients with recurrent spontaneous abortion than in controls.…”

Abortions in First Trimester Pregnancy, Management, Treatment

“…It appears that combining aspirin and heparin has the best results. Patients should start taking heparin as early as possible when pregnant and continue until labor and during puerperium [42][43][44][45][46][47][48][49][50]. Combination of aspirin and heparin is associated with better results.…”

“…Heparin subcutaneously, for example, low molecular weight heparin one injection per day may prevent recycling of circulating anti-cardiolipins or suppress the secretion of embryotoxic agents or HLA-related agents. It also reduces the percentage of NK (CD56+/CD16+) cells [46][47][48][49][50]. It has been associated with gestational hypertension and diabetes mellitus and mainly with premature labor and low birth weight neonates.…”

“…It seems that the combination of aspirin and heparin works best. Heparin should be started as soon as possible in pregnancy and should be maintained until the labor and postpartum especially when the risk of thrombosis is high [42][43][44][45][46][47][48][49][50]. Intravenous immunoglobulin therapy IVIG (no superior to the combination of aspirin and heparin) Intravenous injection of high doses of gamma globulin (300-500 mg/kg body weight).…”

“…To avoid the adverse reactions of heparin therapy, it is recommended to add calcium 600 mg twice daily and vitamin D supplementation 400 IU daily to decrease the osteoporosis risk. The platelet count should be weekly examined in the first two weeks after treatment with heparin because bleeding could occur due to heparin induced thrombocytopenia [42][43][44][45][46][47][48][49][50].…”