Investigation of systemic inflammatory response in first trimester pregnancy failure

BACKGROUND: The contribution of local and systemic inflammation to the pathophysiology of sporadic first trimester miscarriages remains unclear. The objective of this study was to investigate the inflammatory response in the circulation of women presenting with first trimester miscarriage. METHODS: Levels of tumour necrosis factor alpha (TNF alpha), TNF receptors 1 and 2, interferon gamma (IFN gamma), interleukin (IL)-6 and IL-10 were assayed using cytometric bead arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35 normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow cytometry was carried out with samples from 17 euploid and 16 aneuploid miscarriages, 18 pregnant controls and 13 NPW. RESULTS: The plasma of women with euploid miscarriage contained significantly higher circulating levels of TNF alpha (P < 0.005), IFN gamma (P < 0.005), IL-6 (P < 0.005) and IL-10 (P < 0.01) than that of pregnant controls, irrespective of gestational age. Significantly (P < 0.05) higher TNF-R1 levels at 6-9 weeks, and significantly higher TNF alpha/IL-6 (P < 0.001) and significantly lower TNF alpha/IL-10 (P < 0.001) and IFN gamma/IL-10 (P < 0.001) ratios at 10-14 weeks, were also found in euploid miscarriage cases compared with pregnant controls. TNF alpha/IL-10 ratio in plasma was significantly (P < 0.05) lower in miscarriages with an abnormal karyotype than those with normal karyotype. Normal pregnant women had a significantly higher plasma level of IFN gamma (P < 0.01) and IFN gamma/IL-10 ratio (P < 0.005), a significantly (P < 0.005) lower TNF-R1 level, and a significant (P < 0.05) increase in stimulated TNF alpha in monocytes, compared with NPW. CONCLUSIONS: Our data confirm that there is an inflammatory reaction in normal pregnancy compared with the non-pregnant state, which may be disrupted during miscarriage.