Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy

Zübeyde Emiralioğlu Çakır; İbrahim Ömeroğlu; Dilara Ekici Zincirci; İlayda Gercik Arzık; Raziye Torun; Burcu Ceren Özdoğan; Hasan Baran Livdumlu; Hakan Gölbaşı

Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy

Abstract

Aims: To evaluate trimester-specific changes in hematologic inflammatory indices in pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP) and to determine their potential discriminative performance. Methods: This retrospective case–control study included 84 pregnancies with ICP and 96 healthy controls. Complete blood count parameters obtained in each trimester were used to calculate neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), Systemic Immune-inflammation Index (SII), Systemic Inflammation Response Index (SIRI), pan-immune-inflammation value (PIV), and mean platelet volume (MPV). Groups were compared using appropriate statistical tests. Receiver operating characteristic (ROC) analysis was performed to assess the discriminatory performance of first-trimester indices. Results: Third-trimester body mass index, gestational age at delivery, and birth weight differed significantly between groups (p≤0.001). In trimester-based comparisons, first-trimester neutrophil count, platelet count, NLR, and SII were significantly higher in the ICP group (p=0.042; p=0.011; p=0.005; and p=0.028, respectively). Second-trimester hemoglobin and neutrophil counts were modestly increased in ICP (p=0.038 and p=0.022). In the third trimester, only MPV was significantly elevated in the ICP group (p<0.001). ROC analysis demonstrated modest discriminatory ability for first-trimester NLR (AUC=0.621; p=0.005) and SII (AUC=0.595; p=0.028), whereas other indices were not significant. Conclusion: Selected inflammatory indices demonstrate trimester-specific associations with ICP. Elevated first-trimester NLR and SII and increased third-trimester MPV may reflect gestational stage-dependent immune activation; however, their overall discriminative performance remains limited. These markers may serve as supportive but not standalone diagnostic tools.

Keywords

Supporting Institution

The authors received no financial support for this study.

Ethical Statement

Ethical approval for the study was obtained from the local Ethics Committee (protocol number:2025/406, approval date: 13,08,2025).

Thanks

The authors thank the medical and laboratory staff of Izmir City Hospital for their assistance in routine clinical data collection.

References

Çallıoğlu N, Tuna G, Tandoğan Ö, Ersan F, Atalay S, Bilirer KK. Systemic Immune-inflammatory Index and platelet-to-lymphocyte ratio in intrahepatic cholestasis of pregnancy. Saudi Med J. 2024;45(11):1217-1222. doi:10.15537/SMJ.2024.45.11.20240760
Mathur D, Morgan M, McKenzie J, Wakefield D, Janicki MB, Figueroa R. Intrahepatic cholestasis of pregnancy: dilemma in diagnosis and management. J Matern Fetal Neonatal Med. 2022;35(25):8975-8981. doi:10.1080/14767058.2021.2008896
İpek G, Tanaçan A, Peker A, Ağaoğlu Z, Kara Ö, Şahin D. Systemic Inflammation Response Index as a diagnostic and prognostic predictor of intrahepatic cholestasis of pregnancy: a case–control study from a tertiary center. Int J Gynecol Obstet. 2024;165(2):717-722. doi:10.1002/ijgo.15216
Oztas E, Erkenekli K, Ozler S, et al. Can routine laboratory parameters predict adverse pregnancy outcomes in intrahepatic cholestasis of pregnancy? J Perinat Med. 2015;43(6):667-674. doi:10.1515/jpm-2014-0207
Özkan S, Aksan A, Kurt D, et al. Are Systemic inflammation markers reliable for diagnosing intrahepatic cholestasis of pregnancy? A retrospective cohort study. Am J Reprod Immunol. 2024;92(4):e13937. doi:10.1111/aji.13937
Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2014;124(1):120-133. doi:10.1097/AOG.0000000000000346
McIlvride S, Dixon PH, Williamson C. Bile acids and gestation. Mol Aspects Med. 2017;56:90-100. doi:10.1016/j.mam.2017.05.003
Abide ÇY, Vural F, Kılıççı Ç, et al. Can we predict severity of intrahepatic cholestasis of pregnancy using inflammatory markers? Turk J Obstet Gynecol. 2017;14(3):160-165. doi:10.4274/tjod.67674

Silva J, Magenta M, Sisti G, Serventi L, Gaither K. Association between complete blood count components and intrahepatic cholestasis of pregnancy. Cureus. 2020;12(12):8-13. doi:10.7759/cureus.12381
Ergani SY, Celen S. Role of Systemic Immune-inflammatory Index to predict intrahepatic cholestasis of pregnancy. Clin Lab. 2024;70(3):555-561. doi:10.7754/Clin.Lab.2023.231211
Gao XX, Ye MY, Liu Y, et al. Prevalence and risk factors of intrahepatic cholestasis of pregnancy in a Chinese population. Sci Rep. 2020;10(1): 16307. doi:10.1038/s41598-020-73378-5
Gok K, Takmaz T, Kose O, et al. Can first-trimester aspartate aminotransferase/platelet ratio index score predict intrahepatic cholestasis of pregnancy? Hepatol Forum. 2023;4(1):30-34. doi:10.14744/hf.2022.2022.0031
Jafarei RM, Moramezi F, Kargarzadeh E, et al. Maternal and fetal outcomes in mothers with intrahepatic cholestasis of pregnancy compared to healthy pregnant women: a case-control study. Shiraz E-Med J 2025 26:12. 2025;26(12):e163163. doi:10.5812/semj-163163
Li P, Jiang Y, Xie M, et l-al. Factors associated with intrahepatic cholestasis of pregnancy and its influence on maternal and infant outcomes. Medicine. 2023;102(1):E32586. doi:10.1097/MD.0000000000032586
Shan D, Dong R, Hu Y. Current understanding of autophagy in intrahepatic cholestasis of pregnancy. Placenta. 2021;115(20):53-59. doi:10.1016/j.placenta.2021.09.014
Chen L, Li J, You Y, et al. Secreted proteins in plasma and placenta as novel non-invasive biomarkers for intrahepatic cholestasis of pregnancy: a case-control study. Heliyon. 2023;9(11):e21616. doi:10.1016/j.heliyon.2023.e21616
Luo M, Wang L, Yao H, et al. Diagnostic and prognostic value of blood inflammation and biochemical indicators for intrahepatic cholestasis of pregnancy in Chinese pregnant women. Sci Rep. 2022;12(1):1-9. doi:10.1038/s41598-022-22199-9
Biberoglu E, Kirbas A, Daglar K, et al. Role of inflammation in intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Res. 2016;42(3): 252-257. doi:10.1111/jog.12902
Allen K, Jaeschke H, Copple BL. Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Am J Pathol. 2011;178(1):175-186. doi:10.1016/j.ajpath.2010.11.026
Kebapcilar AG, Taner CE, Kebapcilar L, Bozkaya G. High mean platelet volume, low-grade systemic coagulation, and fibrinolytic activation are associated with pre-term delivery and low APGAR score in intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med. 2010;23(10):1205-1210. doi:10.3109/14767051003653278
Kirbas A, Biberoglu E, Daglar K, et al. Neutrophil-to-lymphocyte ratio as a diagnostic marker of intrahepatic cholestasis of pregnancy. Eur J Obstet Gynecol Reprod Biol. 2014;180(1):12-15. doi:10.1016/j.ejogrb.2014.05.042
Liu H, Zhang L, Luo X, Li J, Huang S, Qi H. Prediction of late-onset fetal growth restriction by umbilical artery velocities at 37 weeks of gestation: a cross-sectional study. BMJ Open. 2022;12(8):e060620. doi:10.1136/BMJOPEN-2021-060620
Qi Q, Zhuang L, Shen Y, et al. A novel Systemic Inflammation Response Index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy. Cancer. 2016;122(14):2158-2167. doi:10.1002/cncr.30057
Hrubaru I, Motoc A, Moise ML, et al. The predictive role of maternal biological markers and inflammatory scores NLR, PLR, MLR, SII, and SIRI for the risk of preterm delivery. J Clin Med. 2022;11(23):6982. doi:10.3390/jcm11236982
Fang J, Lin Y, Chen Z, Lin Y, Pan M. The association of inflammatory markers with maternal-neonatal outcome after cervical cerclage. J Inflamm Res. 2023;16:245-255. doi:10.2147/JIR.S393666
Zhang Y, Yue Y, Sun Z, et al. Pan-Immune-Inflammation Value and its association with all-cause and cause-specific mortality in the general population: a nationwide cohort study. Front Endocrinol (Lausanne). 2025;16:1534018. doi:10.3389/fendo.2025.1534018
Yin S, Wan H, Zhang Y, Zhu M, Wang Z, Cui Z. Pan-Immune-Inflammation Value and risk of hypertensive disorders of pregnancy: a cross-sectional study. J Inflamm Res. 2025;18:8049-8063. doi:10.2147/JIR.S533109
Jiang R, Hua Y, Hu X, Hong Z. The Pan Immune Inflammatory Value in relation to non-alcoholic fatty liver disease and hepatic fibrosis. Clin Res Hepatol Gastroenterol. 2024;48(7):102393. doi:10.1016/j.clinre.2024.102393
Dereli ML, Sucu S, Kurt DS, et al. Systemic Immune Inflammation Index, Systemic Inflammatory Response Index and Pan-Immune Inflammation Value in the prediction of idiopathic late-onset fetal growth restriction. Cytokine. 2026;198:157081. doi:10.1016/j.cyto.2025.157081
Akay A, Akdaş Reis Y, Yilmaz Ergani S, et al. An assessment of the relationship between fetal growth restriction and maternal serum markers of systemic inflammation (NLR, SIRI, SII, and PIV). Niger J Clin Pract. 2025;28(4):545-551. doi:10.4103/njcp.njcp_530_24
Aktemur G, Çakır BT, Karabay G, et al. Second-trimester inflammatory markers in predicting fetal growth restriction: a retrospective analysis. Am J Reprod Immunol. 2025;93(1):e70047. doi:10.1111/aji.70047
Zhu Y, Zhang Y, Hu W, et al. First-trimester Pan-Immune-Inflammation Value predicts preeclampsia in a dose-dependent linear pattern. BMC Pregnancy Childbirth. 2025;25(1):1250. doi:10.1186/s12884-025-08406-1
Kurt D, Yilmaz A. Inflammatory hematologic indices in intrahepatic cholestasis of pregnancy: a retrospective case-control study focusing on the aggregate Index of Systemic Inflammation. BMC Pregnancy Childbirth. 2026;26(1):366. doi:10.1186/S12884-026-08860
Brenøe JE, van Hoorn EGM, Beck L, et al. Altered placental macrophage numbers and subsets in pregnancies complicated with intrahepatic cholestasis of pregnancy (ICP) compared to healthy pregnancies. Placenta. 2024;153:22-30. doi:10.1016/J.PLACENTA.2024.05.129

Details

Primary Language

English

Subjects

Obstetrics and Gynaecology

Journal Section

Research Article

Authors

Zübeyde Emiralioğlu Çakır ^*
0000-0001-8298-8363
Türkiye

İbrahim Ömeroğlu
0000-0001-9200-0208
Türkiye

Dilara Ekici Zincirci
0000-0001-7702-0227
Türkiye

İlayda Gercik Arzık
0000-0001-7308-352X
Türkiye

Raziye Torun
0000-0002-0272-7196
Türkiye

Burcu Ceren Özdoğan
0000-0002-6413-1777
Türkiye

Hasan Baran Livdumlu
0009-0008-0210-2146
Türkiye

Hakan Gölbaşı
0000-0001-8682-5537
Türkiye

Publication Date

August 15, 2026

Submission Date

June 4, 2026

Acceptance Date

July 4, 2026

Published in Issue

Year 2026 Volume: 7 Number: 4

IZ

https://izlik.org/JA95FM86BG

Cite

RIS / Bibtex

APA

Emiralioğlu Çakır, Z., Ömeroğlu, İ., Ekici Zincirci, D., Gercik Arzık, İ., Torun, R., Özdoğan, B. C., Livdumlu, H. B., & Gölbaşı, H. (2026). Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy. Journal of Medicine and Palliative Care, 7(4), 739-747. https://izlik.org/JA95FM86BG

AMA

1.Emiralioğlu Çakır Z, Ömeroğlu İ, Ekici Zincirci D, et al. Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy. J Med Palliat Care / JOMPAC / jompac. 2026;7(4):739-747. https://izlik.org/JA95FM86BG

Chicago

Emiralioğlu Çakır, Zübeyde, İbrahim Ömeroğlu, Dilara Ekici Zincirci, et al. 2026. “Comprehensive Assessment of Hematologic Inflammatory Indices across All Trimesters in Intrahepatic Cholestasis of Pregnancy”. Journal of Medicine and Palliative Care 7 (4): 739-47. https://izlik.org/JA95FM86BG.

EndNote

Emiralioğlu Çakır Z, Ömeroğlu İ, Ekici Zincirci D, Gercik Arzık İ, Torun R, Özdoğan B C, Livdumlu HB, Gölbaşı H (August 1, 2026) Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy. Journal of Medicine and Palliative Care 7 4 739–747.

IEEE

[1]Z. Emiralioğlu Çakır et al., “Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy”, J Med Palliat Care / JOMPAC / jompac, vol. 7, no. 4, pp. 739–747, Aug. 2026, [Online]. Available: https://izlik.org/JA95FM86BG

ISNAD

Emiralioğlu Çakır, Zübeyde - Ömeroğlu, İbrahim - Ekici Zincirci, Dilara - Gercik Arzık, İlayda - Torun, Raziye - Özdoğan, Burcu Ceren - Livdumlu, Hasan Baran - Gölbaşı, Hakan. “Comprehensive Assessment of Hematologic Inflammatory Indices across All Trimesters in Intrahepatic Cholestasis of Pregnancy”. Journal of Medicine and Palliative Care 7/4 (August 1, 2026): 739-747. https://izlik.org/JA95FM86BG.

JAMA

1.Emiralioğlu Çakır Z, Ömeroğlu İ, Ekici Zincirci D, Gercik Arzık İ, Torun R, Özdoğan B C, Livdumlu HB, Gölbaşı H. Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy. J Med Palliat Care / JOMPAC / jompac. 2026;7:739–747.

MLA

Emiralioğlu Çakır, Zübeyde, et al. “Comprehensive Assessment of Hematologic Inflammatory Indices across All Trimesters in Intrahepatic Cholestasis of Pregnancy”. Journal of Medicine and Palliative Care, vol. 7, no. 4, Aug. 2026, pp. 739-47, https://izlik.org/JA95FM86BG.

Vancouver

1.Zübeyde Emiralioğlu Çakır, İbrahim Ömeroğlu, Dilara Ekici Zincirci, İlayda Gercik Arzık, Raziye Torun, Burcu Ceren Özdoğan, Hasan Baran Livdumlu, Hakan Gölbaşı. Comprehensive assessment of hematologic inflammatory indices across all trimesters in intrahepatic cholestasis of pregnancy. J Med Palliat Care / JOMPAC / jompac [Internet]. 2026 Aug. 1;7(4):739-47. Available from: https://izlik.org/JA95FM86BG