Research Article
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The relationship between first trimester systemic inflammatory markers and elevated uterine artery pulsatility index

Year 2023, Volume: 8 Issue: 5, 134 - 139, 12.10.2023
https://doi.org/10.22391/fppc.1349107

Abstract

Introduction: Preeclampsia is a serious complication of pregnancy leading to maternal and perinatal morbidity and mortality. The etiopathogenesis still remains unsolved, however, various theories currently become well-proved. The leading etiopathogenetic mechanisms are impaired placentation, and placental hypoxia, immune mechanisms, systemic inflammatory reaction, endothelial damage and maternal cardiovascular maladaptation. These mechanisms overlap and induce each other. There are some preventive interventions only if the patients at high-risk are identified timely. This study aimed to investigate the relationship between the inflammatory pathway and placental insufficiency in the first trimester, utilizing the clinical markers of both. It also aims to find out a cheap and easy test to identify those who absolutely need to undergo a comprehensive risk assessment.
Methods: This retrospective observational study included 28 patients with high uterine artery resistance (pulsatility index >90th centile) in the first trimester as study group and 67 patients with normal uterine artery resistance in the first trimester as control group. The two groups were compared in terms of risk factors for preeclampsia. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio as systemic inflammatory markers were compared between the groups. ROC analysis was performed to obtain a cut-off value for predicting high uterine artery pulsatility index.
Results: Demographic data, anamnestic and examination risk factors for preeclampsia did not differ between the groups. However, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher in the patients with uterine artery pulsatility index above 90th centile. A cut off value of 3.58 and 136.9 of Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, respectively were determined for predicting first trimester uterine artery pulsatility index above 90th centile.
Conclusions: Neutrophil/lymphocyte and platelet/lymphocyte ratio can simply be used to identify the patients who need referral for uterine artery doppler assessment.
Keywords: preeclampsia, uterine artery, pulsatil flow, neutrophil, lymphocyte, placenta

Ethical Statement

Ethics committee of Health Sciences University, Zeynep Kamil Women and Children Diseases Research Hospital approved the study. Application title: ‘Investigating the impact of hemorheological parameters on development of preeclampsia in the patients at high risk’. Decision number 7 (date:11.01.2023).

References

  • 1. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009;33(3):130–7. https://doi.org/10.1053/j.semperi.2009.02.010
  • 2. Von Dadelszen P, Syngelaki A, Akolekar R, Magee LA, Nicolaides KH. Preterm and term pre‐eclampsia: Relative burdens of maternal and perinatal complications. BJOG 2023;130(5):524–30. https://doi.org/10.1111/1471-0528.17370
  • 3. Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, et al. The etiology of preeclampsia. Am J Obstet Gynecol 2022;226(2):844–66. https://doi.org/10.1016/j.ajog.2021.11.1356
  • 4. Albrecht ED, Pepe GJ. Regulation of uterine spiral artery remodeling: a review. Reprod Sci 2020;27(10):1932–42. https://doi.org/10.1007/s43032-020-00212-8
  • 5. Khong SL, Kane SC, Brennecke SP, da Silva Costa F. First-trimester uterine artery doppler analysis in the prediction of later pregnancy complications. Dis Markers 2015;2015:1–10. https://doi.org/10.1155/2015/679730
  • 6. Thuring A, Maršál K, Laurini R. Placental ischemia and changes in umbilical and uteroplacental arterial and venous hemodynamics. J Matern Fetal Neonatal Med 2012;25(6):750–5. https://doi.org/10.3109/14767058.2011.594466
  • 7. Velauthar L, Plana MN, Kalidindi M, Zamora J, Thilaganathan B, Illanes SE, et al. First-trimester uterine artery Doppler and adverse pregnancy outcome: a meta-analysis involving 55,974 women. Ultrasound Obstet Gynecol 2014;43(5):500–7. https://doi.org/10.1002/uog.13275
  • 8. Plasencia W, Maiz N, Poon L, Yu C, Nicolaides KH. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol 2008;32(2):138–46. https://doi.org/10.1002/uog.5402
  • 9. Buonacera A, Stancanelli B, Colaci M, Malatino L. Neutrophil to lymphocyte ratio: An emerging marker of the relationships between the ımmune system and diseases. Int J Mol Sci 2022;23(7):3636. https://doi.org/10.3390/ijms23073636
  • 10. Xue J, Ma D, Jiang J, Liu Y. Diagnostic and prognostic value of immune/inflammation biomarkers for venous thromboembolism: Is it reliable for clinical practice? J Inflamm Res 2021;14:5059–77. https://doi.org/10.2147/JIR.S327014
  • 11. Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: Facts and controversies. Placenta 2006;27(9–10):939–58. https://doi.org/10.1016/j.placenta.2005.12.006
  • 12. Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci 2011;1221(1):80–7. https://doi.org/10.1111/j.1749-6632.2010.05938.x
  • 13. Lee S, Shin J,Kim JS, Shin J, Lee SK, Park HW. Targeting TBK1 attenuates LPS-induced NLRP3 inflammasome activation by regulating of mTORC1 pathways in trophoblasts. Front Immunol 2021;9(12):743700. https://doi.org/10.3389/fimmu.2021.743700
  • 14. Banerjee S, Huang Z, Wang Z, Nakashima A, Saito S, Sharma S, et al. Etiological value of sterile inflammation in preeclampsia: Is it a non-infectious pregnancy complication? Front Cell Infect Microbiol 2021;16(11):694298. https://doi.org/10.3389/fcimb.2021.694298
  • 15. Michalczyk M, Celewicz A, Celewicz M, Woźniakowska-Gondek P, Rzepka R. the role of inflammation in the pathogenesis of preeclampsia. Mediators Inflamm 2020;5:1–9. https://doi.org/10.1155/2020/3864941
  • 16. Tenório MB, Ferreira RC, Moura FA, Bueno NB, de Oliveira ACM, Goulart MOF. Cross-talk between oxidative stress and inflammation in preeclampsia. Oxid Med Cell Longev 2019;4:1–26. https://doi.org/10.1155/2019/8238727
  • 17. Cornelius DC. Preeclampsia: From inflammation to immunoregulation. Clin Med Insights Blood Disord 2018;1(11):1179545X17752325. https://doi.org/10.1177/1179545x17752325
  • 18. Dekker G, Scioscia M, Saito S. Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia. Am J Obstet Gynecol 2022;226(2):867–75. https://doi.org/10.1016/j.ajog.2021.11.019
  • 19. Oglak SC, Tunc S, Olmez F. First trimester mean platelet volume, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio values are useful markers for predicting preeclampsia. Ochsner J 2021;21(4):364–70. https://doi.org/10.31486/toj.21.0026
  • 20. Mannaerts D, Heyvaert S, De Cordt C, Macken C, Loos C, Jacquemyn Y. Are neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and/or mean platelet volume (MPV) clinically useful as predictive parameters for preeclampsia? J Matern Fetal Neonatal Med 2019;32(9):1412–9. https://doi.org/10.1080/14767058.2017.1410701
  • 21. Wang J, Zhu QW, Cheng XY, Liu JY, Zhang LL, Tao YM, et al. Assessment efficacy of neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio in preeclampsia. J Reprod Immunol 2019;132:29–34. https://doi.org/10.1016/j.jri.2019.02.001
  • 22. Poon LC, Shennan A, Hyett JA, Kapur A, Hadar E, Divakar H, et al. The international federation of gynecology and obstetrics ( FIGO) initiative on pre‐eclampsia: A pragmatic guide for first‐trimester screening and prevention. Int J Gynaecol Obstet 2019;145:(Suppl 1):1-33. https://doi.org/10.1002/ijgo.12802
  • 23. Rolnik DL, Wright D, Poon LC, O’Gorman N, Syngelaki A, de Paco Matallana C, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017;377(7):613–22. https://doi.org/10.1056/nejmoa1704559

Gebeliğin birinci trimesterinde sistemik inflamatuar belirteçler ile yüksek uterin arter pulsatilite indeksi ilişkisi

Year 2023, Volume: 8 Issue: 5, 134 - 139, 12.10.2023
https://doi.org/10.22391/fppc.1349107

Abstract

Giriş: Preeklampsi, gebeliğin ciddi bir komplikasyonudur ve maternal ve perinatal morbidite ve mortalitenin önde gelen nedenlerindendir. Etiyopatogenez hala çözülememiştir, ancak çeşitli teoriler artık iyice kanıtlanmıştır. Başlıca etyopatogenetik mekanizmalar defektif plasentasyon, plasental hipoksi, immün mekanizmalar, sistemik inflamatuar reaksiyon, endotel hasarı ve annenin gebeliğe kardiyovasküler maladaptasyonudur. Bu mekanizmalar birbiriyle örtüşür ve birbirini tetikler. Yüksek riskli hastaların zamanında tespit edilmesi durumunda işe yarayabilecek bazı önleyici müdahaleler mevcuttur. Bu çalışma, her ikisinin de klinik belirteçlerini kullanarak, ilk trimesterde inflamatuar yolak ile plasental yetmezlik arasındaki ilişkiyi araştırmayı amaçladı. Ayrıca kapsamlı bir risk değerlendirmesinden geçmesi gereken kişileri tespit etmek için ucuz ve kolay bir test bulmayı da amaçladı.
Yöntem: Bu retrospektif gözlemsel çalışmaya, ilk trimesterde uterin arter direnci yüksek (pulsatilite indeksi >90. persantil) olan 28 hasta çalışma grubu olarak ve ilk trimesterde uterin arter direnci normal olan 67 hasta kontrol grubu olarak dahil edildi. İki grup preeklampsi risk faktörleri açısından karşılaştırıldı. Sistemik inflamatuar belirteçlerden nötrofil/lenfosit oranı ve trombosit/lenfosit oranı gruplar arasında karşılaştırıldı. Yüksek uterin arter pulsatilite indeksini öngörmek için bir kesim değeri elde etmek amacıyla ROC analizi yapıldı.
Bulgular: Preeklampsiye ilişkin demografik veriler, anamnez ve muayeneye dayalı risk faktörleri gruplar arasında farklılık göstermedi. Ancak uterin arter pulsatilite indeksi 90. persantilin üzerinde olan hastalarda nötrofil/lenfosit oranı ve trombosit/lenfosit oranı anlamlı olarak yüksekti. Birinci trimester uterin arter pulsatilite indeksinin 90. persantilin üzerinde olduğunu predikte edebilecek nötrofil/lenfosit oranı ve trombosit/lenfosit oranının sırasıyla 3,58 ve 136,9 kesme değeri olduğu belirlendi.
Sonuç: Nötrofil/lenfosit ve trombosit/lenfosit oranı, uterin arter doppler değerlendirmesi için sevk edilmesi gereken hastaların belirlenmesinde basitçe kullanılabilir.
Anahtar Kelimeler: preeklampsi, uterin arter, pulsatil akım, nötrofil, lenfosit, plasenta

Ethical Statement

Ethics committee of Health Sciences University, Zeynep Kamil Women and Children Diseases Research Hospital approved the study. Application title: ‘Investigating the impact of hemorheological parameters on development of preeclampsia in the patients at high risk’. Decision number 7 (date:11.01.2023).

References

  • 1. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009;33(3):130–7. https://doi.org/10.1053/j.semperi.2009.02.010
  • 2. Von Dadelszen P, Syngelaki A, Akolekar R, Magee LA, Nicolaides KH. Preterm and term pre‐eclampsia: Relative burdens of maternal and perinatal complications. BJOG 2023;130(5):524–30. https://doi.org/10.1111/1471-0528.17370
  • 3. Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, et al. The etiology of preeclampsia. Am J Obstet Gynecol 2022;226(2):844–66. https://doi.org/10.1016/j.ajog.2021.11.1356
  • 4. Albrecht ED, Pepe GJ. Regulation of uterine spiral artery remodeling: a review. Reprod Sci 2020;27(10):1932–42. https://doi.org/10.1007/s43032-020-00212-8
  • 5. Khong SL, Kane SC, Brennecke SP, da Silva Costa F. First-trimester uterine artery doppler analysis in the prediction of later pregnancy complications. Dis Markers 2015;2015:1–10. https://doi.org/10.1155/2015/679730
  • 6. Thuring A, Maršál K, Laurini R. Placental ischemia and changes in umbilical and uteroplacental arterial and venous hemodynamics. J Matern Fetal Neonatal Med 2012;25(6):750–5. https://doi.org/10.3109/14767058.2011.594466
  • 7. Velauthar L, Plana MN, Kalidindi M, Zamora J, Thilaganathan B, Illanes SE, et al. First-trimester uterine artery Doppler and adverse pregnancy outcome: a meta-analysis involving 55,974 women. Ultrasound Obstet Gynecol 2014;43(5):500–7. https://doi.org/10.1002/uog.13275
  • 8. Plasencia W, Maiz N, Poon L, Yu C, Nicolaides KH. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol 2008;32(2):138–46. https://doi.org/10.1002/uog.5402
  • 9. Buonacera A, Stancanelli B, Colaci M, Malatino L. Neutrophil to lymphocyte ratio: An emerging marker of the relationships between the ımmune system and diseases. Int J Mol Sci 2022;23(7):3636. https://doi.org/10.3390/ijms23073636
  • 10. Xue J, Ma D, Jiang J, Liu Y. Diagnostic and prognostic value of immune/inflammation biomarkers for venous thromboembolism: Is it reliable for clinical practice? J Inflamm Res 2021;14:5059–77. https://doi.org/10.2147/JIR.S327014
  • 11. Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: Facts and controversies. Placenta 2006;27(9–10):939–58. https://doi.org/10.1016/j.placenta.2005.12.006
  • 12. Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci 2011;1221(1):80–7. https://doi.org/10.1111/j.1749-6632.2010.05938.x
  • 13. Lee S, Shin J,Kim JS, Shin J, Lee SK, Park HW. Targeting TBK1 attenuates LPS-induced NLRP3 inflammasome activation by regulating of mTORC1 pathways in trophoblasts. Front Immunol 2021;9(12):743700. https://doi.org/10.3389/fimmu.2021.743700
  • 14. Banerjee S, Huang Z, Wang Z, Nakashima A, Saito S, Sharma S, et al. Etiological value of sterile inflammation in preeclampsia: Is it a non-infectious pregnancy complication? Front Cell Infect Microbiol 2021;16(11):694298. https://doi.org/10.3389/fcimb.2021.694298
  • 15. Michalczyk M, Celewicz A, Celewicz M, Woźniakowska-Gondek P, Rzepka R. the role of inflammation in the pathogenesis of preeclampsia. Mediators Inflamm 2020;5:1–9. https://doi.org/10.1155/2020/3864941
  • 16. Tenório MB, Ferreira RC, Moura FA, Bueno NB, de Oliveira ACM, Goulart MOF. Cross-talk between oxidative stress and inflammation in preeclampsia. Oxid Med Cell Longev 2019;4:1–26. https://doi.org/10.1155/2019/8238727
  • 17. Cornelius DC. Preeclampsia: From inflammation to immunoregulation. Clin Med Insights Blood Disord 2018;1(11):1179545X17752325. https://doi.org/10.1177/1179545x17752325
  • 18. Dekker G, Scioscia M, Saito S. Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia. Am J Obstet Gynecol 2022;226(2):867–75. https://doi.org/10.1016/j.ajog.2021.11.019
  • 19. Oglak SC, Tunc S, Olmez F. First trimester mean platelet volume, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio values are useful markers for predicting preeclampsia. Ochsner J 2021;21(4):364–70. https://doi.org/10.31486/toj.21.0026
  • 20. Mannaerts D, Heyvaert S, De Cordt C, Macken C, Loos C, Jacquemyn Y. Are neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and/or mean platelet volume (MPV) clinically useful as predictive parameters for preeclampsia? J Matern Fetal Neonatal Med 2019;32(9):1412–9. https://doi.org/10.1080/14767058.2017.1410701
  • 21. Wang J, Zhu QW, Cheng XY, Liu JY, Zhang LL, Tao YM, et al. Assessment efficacy of neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio in preeclampsia. J Reprod Immunol 2019;132:29–34. https://doi.org/10.1016/j.jri.2019.02.001
  • 22. Poon LC, Shennan A, Hyett JA, Kapur A, Hadar E, Divakar H, et al. The international federation of gynecology and obstetrics ( FIGO) initiative on pre‐eclampsia: A pragmatic guide for first‐trimester screening and prevention. Int J Gynaecol Obstet 2019;145:(Suppl 1):1-33. https://doi.org/10.1002/ijgo.12802
  • 23. Rolnik DL, Wright D, Poon LC, O’Gorman N, Syngelaki A, de Paco Matallana C, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017;377(7):613–22. https://doi.org/10.1056/nejmoa1704559

Details

Primary Language English
Subjects Obstetrics and Gynaecology
Journal Section Original Research
Authors

Lutfiye UYGUR 0000-0002-6325-1910

Publication Date October 12, 2023
Submission Date August 24, 2023
Acceptance Date October 11, 2023
Published in Issue Year 2023Volume: 8 Issue: 5

Cite

APA UYGUR, L. (2023). The relationship between first trimester systemic inflammatory markers and elevated uterine artery pulsatility index. Family Practice and Palliative Care, 8(5), 134-139. https://doi.org/10.22391/fppc.1349107
AMA UYGUR L. The relationship between first trimester systemic inflammatory markers and elevated uterine artery pulsatility index. Fam Pract Palliat Care. October 2023;8(5):134-139. doi:10.22391/fppc.1349107
Chicago UYGUR, Lutfiye. “The Relationship Between First Trimester Systemic Inflammatory Markers and Elevated Uterine Artery Pulsatility Index”. Family Practice and Palliative Care 8, no. 5 (October 2023): 134-39. https://doi.org/10.22391/fppc.1349107.
EndNote UYGUR L (October 1, 2023) The relationship between first trimester systemic inflammatory markers and elevated uterine artery pulsatility index. Family Practice and Palliative Care 8 5 134–139.
IEEE L. UYGUR, “The relationship between first trimester systemic inflammatory markers and elevated uterine artery pulsatility index”, Fam Pract Palliat Care, vol. 8, no. 5, pp. 134–139, 2023, doi: 10.22391/fppc.1349107.
ISNAD UYGUR, Lutfiye. “The Relationship Between First Trimester Systemic Inflammatory Markers and Elevated Uterine Artery Pulsatility Index”. Family Practice and Palliative Care 8/5 (October 2023), 134-139. https://doi.org/10.22391/fppc.1349107.
JAMA UYGUR L. The relationship between first trimester systemic inflammatory markers and elevated uterine artery pulsatility index. Fam Pract Palliat Care. 2023;8:134–139.
MLA UYGUR, Lutfiye. “The Relationship Between First Trimester Systemic Inflammatory Markers and Elevated Uterine Artery Pulsatility Index”. Family Practice and Palliative Care, vol. 8, no. 5, 2023, pp. 134-9, doi:10.22391/fppc.1349107.
Vancouver UYGUR L. The relationship between first trimester systemic inflammatory markers and elevated uterine artery pulsatility index. Fam Pract Palliat Care. 2023;8(5):134-9.

Family Practice and Palliative Care       ISSN 2458-8865       E-ISSN 2459-1505