İlk Trimester Fibrinojen-Albumin Oranının Geç Fetal Gelişim Kısıtlılığı Öngörüsündeki Değeri

Öz

Fetal büyüme kısıtlılığı (FGR), erken ve geç başlangıçlı olmak üzere iki ana gruba ayrılır ve olumsuz perinatal sonuçların yaygın bir nedenidir. İki grup arasında ayrım 32. gebelik haftasına göre yapılmaktadır. Erken gebelik döneminde FGR öngörüsü için yaygın olarak kabul gören bir tarama yöntemi yoktur. Maternal inflamasyon, FGR gelişiminde önemli bir faktördür. İnflamasyon varlığında, fibrinojen seviyeleri artar ve albümin seviyeleri azalır, bu da fibrinojen albümin oranının (FAR) yükselmesine neden olur. FAR'ın inflamasyonla ilişkili çeşitli hastalıklar için değerli bir prognostik belirteç olduğu gösterilmiştir. Bu retrospektif çalışma, geç başlangıçlı FGR gelişimini öngörmede ilk trimester FAR'ın değerini araştırmayı amaçlamıştır. Çalışmada ilk trimester CRP, fibrinojen ve FAR değerlerinin FGR grubunda istatistiksel olarak anlamlı derecede yüksek olduğu bulunmuştur (tümü için p<0,001). ROC eğrisi analizleri, hem CRP hem de FAR'ın geç FGR gelişimi için istatistiksel olarak anlamlı şekilde prediktif performans sergilediğini göstermiştir. Bununla birlikte, konvansiyonel bir inflamatuar belirteç olan “CRP ”nin FGR'yi öngörme performansı (duyarlılık:%61, özgüllük:%60) FAR değerinden (duyarlılık:%73, özgüllük:%71) daha düşük bulunmuştur. Ayrıca, FGR grubunda olumsuz yenidoğan sonuçları ve yenidoğan yoğun bakım ünitesine yatış oranları anlamlı şekilde yüksek bulunmuştur. Erken gebelikte FGR riskinin öngörülmesi, uygun gebelik takiplerinin planlanması ve gerekli önleyici stratejilerin uygulanması için çok önemlidir. Bu çalışma ile FAR değerinin geç FGR gelişimini öngörmek için potansiyel bir prognostik belirteç olduğu gösterilmiştir..

Anahtar Kelimeler

• Fetal büyüme kısıtlılığı
• inflamasyon
• fibrinojen-albümin oranı.

The Predictive Value of First Trimester Fibrinogen-Albumin Ratio for Late Onset Fetal Growth Restriction

Öz

Fetal growth restriction (FGR) is a common cause of adverse pregnancy outcomes, with two main categories: early and late onset.The standard cut-off gestational age is 32 weeks.There's no accepted screening method for early pregnancy prediction. Maternal inflammation is a key factor in FGR development. In the context of inflammation, fibrinogen levels increase and albumin levels decrease, resulting in an elevated fibrinogen albumin ratio (FAR). FAR has been shown to be a valuable prognostic marker for various inflammation-related diseases. This retrospective study aimed to investigate the value of first trimester FAR in predicting the development of late-onset FGR. The study found that first trimester CRP, fibrinogen, and FAR values were statistically significantly higher in the FGR group (p<0.001 for all). ROC curve analyses demonstrated that both CRP and FAR exhibited significant predictive capabilities for the development of late FGR. However, the performance of the conventional inflammatory marker “CRP” (sensitivity:61%, specificity:60%) in predicting FGR was found to be inferior to that of FAR (sensitivity:73%, specificity:71%). Also, the FGR group demonstrated significantly elevated rates of adverse neonatal outcomes and neonatal intensive care unit hospitalization. The prediction of FGR risk in early pregnancy is crucial for the implementation of appropriate pregnancy follow-ups and the administration of necessary preventive strategies.This study underscores the potential value of FAR as a prognostic instrument to estimate the probability of late FGR.

Anahtar Kelimeler

• Fetal growth restriction
• inflammation
• fibrinogen-albumin ratio

Kaynakça

1. 1. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics and the Society forMaternal-FetalMedicin. ACOG Practice Bulletin No. 204: Fetal Growth Restriction. Obstet Gynecol. 2019 Feb;133(2):e97–109.
2. 2. Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2016 Sep;48(3):333–9.
3. 3. Nardozza LMM, Caetano ACR, Zamarian ACP, Mazzola JB, Silva CP, Marçal VMG, et al. Fetal growth restriction: current knowledge. Arch Gynecol Obstet. 2017 May;295(5):1061–77.
4. 4. Crovetto F, Triunfo S, Crispi F, Rodriguez-Sureda V, Dominguez C, Figueras F, et al. Differential performance of first-trimester screening in predicting small-for-gestational-age neonate or fetal growth restriction. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2017 Mar;49(3):349–56.
5. 5. Firatligil FB, Sucu ST, Tuncdemir S, Saglam E, Dereli ML, Ozkan S, et al. Evaluation of systemic immune-inflammation index for predicting late-onset fetal growth restriction. Arch Gynecol Obstet. 2024 Jul;310(1):433–9.
6. 6. Kırmızı DA, Baser E, Onat T, Caltekin MD, Kara M, Yalvac ES. Can Inflammatory Hematological Parameters be a Guide to Late-onset Fetal Growth Restriction? Z Geburtshilfe Neonatol. 2020 Oct;224(5):262–8.
7. 7. Luyendyk JP, Schoenecker JG, Flick MJ. The multifaceted role of fibrinogen in tissue injury and inflammation. Blood. 2019 Feb 7;133(6):511–20.
8. 8. Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J Parenter Enteral Nutr. 2019 Feb;43(2):181–93.

9. 9. Ren H, Liu W, Niu A, Zhao X. Fibrinogen to albumin ratio, a novel serum indicator for evaluating the severity of preeclampsia: A single-center retrospective study. Medicine (Baltimore). 2023 Mar 31;102(13):e33419.
10. 10. Su J, Yang Y, Cao Y, Yin Z. The predictive value of pre-delivery laboratory test results for the severity of placental abruption and pregnancy outcome. Placenta. 2021 Jan 1;103:220–5.
11. 11. Xu Q, Zhu C, Zhang Q, Hu Z, Ji K, Qian L. Association between fibrinogen-to-albumin ratio and prognosis of patients with heart failure. Eur J Clin Invest. 2023 Oct;53(10):e14049.
12. 12. Dong G, Ma T, Xu Z, Zhang M, Hu Y, Yang J, et al. Fibrinogen-to-Albumin Ratio in Neonatal Sepsis. Int J Gen Med. 2023;16:4965–72.
13. 13. Ağaoğlu Z, Tanacan A, Aktaş BA, Karatas E, Okutucu G, Şerbetçi H, et al. Assessment of the Fibrinogen-to-Albumin Ratio in Predicting the Severity of Hyperemesis Gravidarum. Jinekoloji-Obstet Ve Neonatoloji Tıp Derg. 2024 Dec 28;21(4):309–15.
14. 14. Lees CC, Stampalija T, Baschat A, da Silva Costa F, Ferrazzi E, Figueras F, et al. ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2020 Aug;56(2):298–312.
15. 15. Khalil A, Thilaganathan B. Role of uteroplacental and fetal Doppler in identifying fetal growth restriction at term. Best Pract Res Clin Obstet Gynaecol. 2017 Jan;38:38–47.
16. 16. Cignini P, Maggio Savasta L, Gulino FA, Vitale SG, Mangiafico L, Mesoraca A, et al. Predictive value of pregnancy-associated plasma protein-A (PAPP-A) and free beta-hCG on fetal growth restriction: results of a prospective study. Arch Gynecol Obstet. 2016 Jun;293(6):1227–33.
17. 17. Crovetto F, Triunfo S, Crispi F, Rodriguez-Sureda V, Roma E, Dominguez C, et al. First-trimester screening with specific algorithms for early- and late-onset fetal growth restriction. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2016 Sep;48(3):340–8.
18. 18. Hauguel-de Mouzon S, Guerre-Millo M. The placenta cytokine network and inflammatory signals. Placenta. 2006 Aug;27(8):794–8.
19. 19. Vilotić A, Nacka-Aleksić M, Pirković A, Bojić-Trbojević Ž, Dekanski D, Jovanović Krivokuća M. IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. Int J Mol Sci. 2022 Nov 23;23(23):14574.
20. 20. Jena MK, Sharma NR, Petitt M, Maulik D, Nayak NR. Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta. Biomolecules. 2020 Jun 24;10(6):953.
21. 21. Raghupathy R, Al-Azemi M, Azizieh F. Intrauterine growth restriction: cytokine profiles of trophoblast antigen-stimulated maternal lymphocytes. Clin Dev Immunol. 2012;2012:734865.
22. 22. Tonyali NV, Sarsmaz K, Bayraktar B, Kahraman NC, Sucu ST, Aktemur G, et al. Delta neutrophil index (DNI) as a potential biomarker for fetal growth restriction: insights from maternal hematological changes and neonatal outcomes. BMC Pregnancy Childbirth. 2024 Oct 7;24(1):655.
23. 23. Manten GTR, Sikkema JM, Franx A, Hameeteman TM, Visser GHA, de Groot PG, et al. Increased high molecular weight fibrinogen in pre-eclampsia. Thromb Res. 2003;111(3):143–7.
24. 24. Davidson EC, Phillips LL. Coagulation studies in the hypertensive toxemias of pregnancy. Am J Obstet Gynecol. 1972 Aug 1;113(7):905–10.
25. 25. Chen Y, Lin L. Potential Value of Coagulation Parameters for Suggesting Preeclampsia During the Third Trimester of Pregnancy. Am J Med Sci. 2017 Jul;354(1):39–43.
26. 26. Francalanci I, Comeglio P, Liotta AA, Cellai AP, Fedi S, Parretti E, et al. D-Dimer in intra-uterine growth retardation and gestational hypertension. Thromb Res. 1995 Oct 1;80(1):89–92.
27. 27. Tetik K, Seçkin KD, Karslı FM, Sarıaslan S, Çakmak B, Danışman N. Can we use as a marker the maternal serum levels of D-dimer and fibrinogen to predict intra uterin growth restriction? Turk J Obstet Gynecol. 2014 Dec;11(4):228–32.
28. 28. Seong WJ, Chong GO, Hong DG, Lee TH, Lee YS, Cho YL, et al. Clinical significance of serum albumin level in pregnancy-related hypertension. J Obstet Gynaecol Res. 2010 Dec;36(6):1165–73.
29. 29. Özdemir S, Kıyıcı A, Balci O, Göktepe H, Çiçekler H, Çelik Ç. Assessment of ischemia-modified albumin level in patients with recurrent pregnancy loss during the first trimester. Eur J Obstet Gynecol Reprod Biol. 2011 Apr;155(2):209–12.
30. 30. Usta CS, Atik TK, Ozcaglayan R, Bulbul CB, Camili FE, Adali E. Does the fibrinogen/albumin ratio predict the prognosis of pregnancies with abortus imminens? Saudi Med J. 2021 Mar;42(3):255–63.
31. 31. Wu J, Liu X, Qin C, Zhang J, Liu X, Hu J, et al. Effect of maternal serum albumin level on birthweight and gestational age: an analysis of 39200 singleton newborns. Front Endocrinol. 2024 Mar 5;15:1266669.
32. 32. Xiong T, Wu Y, Huang L, Chen X, Zhang Y, Zhong C, et al. Association of the maternal serum albumin level with fetal growth and fetal growth restriction in term-born singletons: a prospective cohort study. Fertil Steril. 2022 Feb;117(2):368–75.
33. 33. Hasin A, Begum R, Khan MR, Ahmed F. Relationship between birth weight and biochemical measures of maternal nutritional status at delivery in Bangladeshi urban poors. Int J Food Sci Nutr. 1996 May;47(3):273–9.
34. 34. Maher JE, Goldenberg RL, Tamura T, Cliver SP, Johnston KE, Hoffman HJ. Indicators of maternal nutritional status and birth weight in term deliveries. Obstet Gynecol. 1993 Feb;81(2):165–9.
35. 35. Dai LL, Chen C, Wu J, Cheng JF, He F. The predictive value of fibrinogen-to-albumin ratio in the active, severe active, and poor prognosis of systemic lupus erythematosus: A single-center retrospective study. J Clin Lab Anal. 2022 Sep;36(9):e24621.
36. 36. Li M, Tang C, Luo E, Qin Y, Wang D, Yan G. Relation of Fibrinogen-to-Albumin Ratio to Severity of Coronary Artery Disease and Long-Term Prognosis in Patients with Non-ST Elevation Acute Coronary Syndrome. BioMed Res Int. 2020;2020:1860268.
37. 37. Liu M, Huang Y, Huang Z, Zhong Z, Deng W, Huang Z, et al. The role of fibrinogen to albumin ratio in ankylosing spondylitis: Correlation with disease activity. Clin Chim Acta Int J Clin Chem. 2020 Jun;505:136–40.
38. 38. Hwang KT, Chung JK, Roh EY, Kim J, Oh S, Kim YA, et al. Prognostic Influence of Preoperative Fibrinogen to Albumin Ratio for Breast Cancer. J Breast Cancer. 2017 Sep;20(3):254–63.
39. 39. Tan Z, Zhang M, Han Q, Wen J, Luo K, Lin P, et al. A novel blood tool of cancer prognosis in esophageal squamous cell carcinoma: the Fibrinogen/Albumin Ratio. J Cancer. 2017;8(6):1025–9.
40. 40. Moffett-King A. Natural killer cells and pregnancy. Nat Rev Immunol. 2002 Sep;2(9):656–63.
41. 41. Sacks GP, Seyani L, Lavery S, Trew G. Maternal C-reactive protein levels are raised at 4 weeks gestation. Hum Reprod Oxf Engl. 2004 Apr;19(4):1025–30.
42. 42. Pitiphat W, Gillman MW, Joshipura KJ, Williams PL, Douglass CW, Rich-Edwards JW. Plasma C-reactive protein in early pregnancy and preterm delivery. Am J Epidemiol. 2005 Dec 1;162(11):1108–13.
43. 43. Laganà AS, Favilli A, Triolo O, Granese R, Gerli S. Early serum markers of pre-eclampsia: are we stepping forward? J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2016 Sep;29(18):3019–23.
44. 44. Nikbakht R, Moghadam EK, Nasirkhani Z. Maternal serum levels of C-reactive protein at early pregnancy to predict fetal growth restriction and preterm delivery: A prospective cohort study. Int J Reprod Biomed. 2020 Mar;18(3):157–64.
45. 45. Erkenekli K, Keskin U, Uysal B, Kurt YG, Sadir S, Çayci T, et al. Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction. J Obstet Gynaecol J Inst Obstet Gynaecol. 2015 Apr;35(3):225–8.
46. 46. Gandevani SB, Banaem LM, Mohamadi B, Moghadam NA, Asghari M. Association of high-sensitivity C-reactive protein serum levels in early pregnancy with the severity of preeclampsia and fetal birth weight. J Perinat Med. 2012 Jun 14;40(6):601–5.