Table Info

Table 5.

Publications on TNF-α, TGF-β, and NLR in recurrent pregnancy loss

Author and year	Title	Ethnicity	Gestational age	Levels
Tumor necrosis factor-alpha (TNF-α)
Beckmann et al. 1997 [24]	Circulating bioactive tumor necrosis factor-alpha, tumor necrosis factor-alpha receptors, fibronectin, and tumor necrosis factor-alpha inducible cell adhesion molecule VCAM-1 in uncomplicated pregnancy	Netherlands	All three gestational ages	↑
Calleja-Agius et al. 2012 [5]	The role of tumor necrosis factor-receptors in pregnancy with normal and adverse outcome	Review	All three gestational ages	↑
Moreli et al. 2012 [25]	Interleukin 10 and tumor necrosis factor-alpha in pregnancy: aspects of interest in clinical obstetric	Brazil	During pregnancy	↑
Azizieh et al. 2015 [27]	Tumor necrosis factor-α and pregnancy complications: a prospective study	Kuwait	All three gestational ages	↑
Siwetz et al. 2016 [6]	TNF-α alters the inflammatory secretion profile of human first trimester placenta	Austria	First trimester	↑
Jang et al. 2016 [29]	Polymorphisms in tumor necrosis factor-alpha (−863C>A, −857C>T and +488G>A) are associated with idiopathic recurrent pregnancy loss in Korean women	Korea	ND	↑
Subha et al. 2016 [23]	Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension	India	All three gestational ages	↑
Alijotas-Reig et al. 2017 [7]	Tumor Necrosis Factor-Alpha and Pregnancy: Focus on Biologics. An Updated and Comprehensive Review	Review	ND	↑
Samudra et al. 2018 [28]	CD39 and CD73 activity are protective in a mouse model of antiphospholipid antibody-induced miscarriages	Mouse model	ND	↑
Begum et al. 2021 [8]	Impact of TNF-α profile in recurrent pregnancy loss pathogenesis	Assam (India)	Term delivery	↑
Spence et al. 2021 [21]	Maternal Serum Cytokine Concentrations in Healthy Pregnancy and Preeclampsia	Review	All three gestational age	↑
Zhong et al. 2022 [4]	Case Report: TNF-Alpha Inhibitors to Rescue Pregnancy in Women With Potential Pregnancy Loss: A Report of Ten Cases	China	First trimester	↑
Dai et al. 2022 [26]	TNF-α/anti-TNF-α drugs and its effect on pregnancy outcomes	China	ND	↑
Present study	Predominant pro-inflammatory environment in mid-gestation pregnant women with history of recurrent pregnancy loss: a South Indian study	South India	Mid-gestation	↑
Transforming growth factor-beta (TGF-β)
Ogasawara et al. 2000 [40]	Elevation of transforming growth factor-beta1 is associated with recurrent miscarriage	ND	ND	↑
Ball et al. 2007 [42]	Expression of TGF beta in the placental bed is not altered in sporadic miscarriage	UK	First and second trimester	No significant difference
Abdulkhaliq et al. 2018 [41]	The Role of IL-6 and TGF-β1 in Iraqi Women with Recurrent Abortion	Iraq	First trimester	↑
Yang et al. 2021 [10]	Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy	China	ND	↓
Dirisipam et al. 2023 [37]	Can circulating levels of transforming growth factor-β1 in early pregnancy serve as a predictive marker of unfavourable outcome?	India	First trimester	↓
Jameel et al. 2024 [36]	Circulating levels of cytokines (IL-6, IL-10 and TGF-β) and CD4⁺CD25⁺FOXP3⁺Treg cell population in recurrent pregnancy loss	India	Second trimester	↓
Mishra et al. 2025 [38]	The Impact of Inflammatory Cytokines on Recurrent Pregnancy Loss: A Preliminary Investigation	India	ND	↓
Present study	Predominant pro-inflammatory environment in mid-gestation pregnant women with history of recurrent pregnancy loss: a South Indian study	South India	Mid-gestation	↓
TNF-α/TGF-β ratio
Raghupathy et al. 1999 [47]	Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions	Kuwait	First trimester	↑
Makhseed et al. 2001 [46]	Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions	Kuwait	First trimester	↑
Kwak-Kim et al. 2003 [44]	Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF	Chicago	First trimester	↑
Peng et al. 2021 [49]	Significance of the ratio interferon-γ/interleukin-4 in early diagnosis and immune mechanism of unexplained recurrent spontaneous abortion	China	ND	↑
Piccinni et al. 2021 [43]	Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction	Review	ND	↑
Madduru et al. 2021 [48]	Association of reduced maternal sHLA-G5 isoform levels and elevated TNF-α/IL-4 cytokine ratio with Recurrent Pregnancy Loss: A study on South Indian women	India	First and second trimester	↑
Raghupathy 2022 [45]	Cytokines and pregnancy complications: modulation for prevention and treatment	Review	First trimester	↑
Present study	Predominant pro-inflammatory environment in mid-gestation pregnant women with history of recurrent pregnancy loss: a South Indian study	South India	Mid-gestation	↑
Neutrophil to lymphocyte ratio (NLR)
Klement et al. 2018 [56]	Neutrophils to lymphocytes ratio and platelets to lymphocytes ratio in pregnancy: A population study	Israel	All three gestational stages	No significant difference
Christoforaki et al. 2020 [57]	First trimester neutrophil to lymphocyte ratio (NLR) and pregnancy outcome	Greece	First trimester	No significant difference
Oğlak and Aydın 2020 [22]	Are neutrophil to lymphocyte ratio and platelet to lymphocyte ratio clinically useful for the prediction of early pregnancy loss?	Turkey	ND	↑
Jiang et al. 2021 [53]	Neutrophil and Neutrophil-to-Lymphocyte Ratio as Clinically Predictive Risk Markers for Recurrent Pregnancy Loss	China	First trimester	↑
Onat et al. 2020 [52]	Can hematologic inflammation markers be the indicator of early pregnancy loss?	Turkey	First trimester	↑
Taskomur and Aydın 2022 [55]	Evaluation of Inflammatory markers in threatened abortions and spontaneous abortions	Turkey	6–20 weeks of gestation	No significant difference
Hantoushzadeh et al. 2024 [54]	Diagnostic value of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio to predict recurrent pregnancy loss and abortion; a systematic review and meta-analysis	Review	First trimester	↑
Present study	Predominant pro-inflammatory environment in mid-gestation pregnant women with history of recurrent pregnancy loss: a South Indian study	South India	Mid-gestation	↑

Matrix table for TNF-α, TGF-β, TNF-α/TGF-β, and NLR. ND: not defined; ↑: high; ↓: low

Declarations

Acknowledgments

We are grateful to the blood donors who have helped us with this study. During the preparation of this work, authors used the Quillbot for improving the readability and fluency of the language. After using the Quillbot, authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Author contributions

RB: Investigation, Methodology, Project administration, Resources, Software, Writing—original draft, Data curation, Formal analysis. SJ: Data curation, Formal analysis. FR: Writing—review & editing. RB: Methodology, Resources. PJ: Conceptualization, Visualization, Writing—original draft, Writing—review & editing. Prior to submission, the work was reviewed and approved by all authors.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was approved by the Institutional Ethical Committee from Osmania Medical College, Hyderabad, Telangana-500028, India (Ethical approval reference no: Reg No: ECR/300/Inst/AP/2013/RR-16).

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable

Availability of data and materials

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Funding

This research was funded by the Indian Council for Medical Research (ICMR ID no. [2019-1022]), New Delhi, India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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