Predominant pro-inflammatory environment in mid-gestation pregnant women with history of recurrent pregnancy loss: a South Indian study

Aim: To assess circulating levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in mid-gestation pregnant women from South India, with (RPL) and without history of recurrent pregnancy loss (non-RPL) and its correlation with neutrophil to lymphocyte ratio (NLR). Methods: Blood samples were collected from 400 pregnant women attending government maternity hospital, Hyderabad, and subjected to enzyme linked immunosorbent assay (ELISA) for cytokines. NLR was calculated from absolute cell counts obtained from hospital records. Mann-Whitney U and Spearman r correlation was conducted as data followed non-normal distribution. Results: We found significantly decreased level of TGF-β and elevated TNF-α, TNF-α/TGF-β (P < 0.0001), and NLR (P = 0.0007) in patients over controls. Receiver operating curve characteristics of TNF-α/TGF-β (area under curve: 0.96) were superior to individual cytokines and NLR for patients when compared to the control group. A negative correlation was noted between NLR and TGF-β in the RPL group (P = 0.0041). Conclusions: Our results are indicative of predominant pro-inflammatory environment during mid-gestation in patients contrary to the anti-inflammatory milieu in controls. This is first study that attempted to connect cytokines with cellular ratio in RPL. The affordability of NLR to track inflammation is promised by its inverse correlation with TGF-β. However, further longitudinal studies are warranted spanning all stages of gestation in normal pregnant and RPL women to establish our observations. The limitations of the study include other factors that drive pro-inflammatory status like emotional dysregulation in women associated with chronic pro-inflammatory status is unexplored.