IS AMNIOTIC FLUID ANALYSIS DURING THE SECOND TRIMESTER A PREDICTOR FOR THE DETECTION OF PRETERM LABOR?

Abstract

Objective: Premature activation of the hypothalamic-pituitary- adrenal axis due to stress can initiate preterm labor. Many mechanisms have been proposed to explain etiopathogenesis. The most important one is clinical and subclinical chorioamnionitis. We aimed to assess the possibility of early detection and prevention of preterm labor based on second trimester amniotic fluid analysis. Materials and Methods: One hundred and twenty-five pregnant women with singleton pregnancies who underwent amniocentesis were included. The first 2 cm3 of the amniotic fluid obtained during the amniocentesis was used for glucose, interleukin- 1, interleukin-6, high sensitivity C-reactive protein, electrolytes, progesterone/estrogen analysis, and cell counts. Results: Sixteen women (13.8%) went into labor prior to 37 weeks of gestation. The mean age of the study population was 33.2±6.25 years. Ages were similar between the preterm and term groups (36.06±3.91 vs 32.77±6.43). Furthermore, the analysis of all parameters in the amniotic fluid did not show any statistical significant difference between the groups. Conclusion: The possible effects of subclinical infection and steroid hormonal changes that are implied in the etiology of preterm labor were investigated in our study, and no evidence was found to support that these factors played a role in the etiology of preterm labor.

Keywords

• Amniocentesis
• preterm labor
• glucose
• interleukin
• high sensitivity C-reactive protein
• leukocyte count

İKİNCİ TRİMESTIRDA BAKILAN AMNİOTİK SIVI ANALİZİ PRETERM DOĞUM ÖNGÖRÜSÜNDE BİR PREDİKTÖR MÜDÜR?

Abstract

Amaç: Strese bağlı hipotalamik-pitüiter-adrenal aksın prematür aktivasyonu preterm doğumu başlatır. Etyopatogenezi açıklamak üzere pek çok mekanizma ileri sürülmüştür. En önemlisi klinik ve subklinik koryoamniyonittir. Preterm eylem riski taşıyan hastaların daha erken dönemde belirlenmesi, önlenmesi ve hastaların yanlış tanı nedeni ile gereksiz yere tokoliz tedavisi almasının önlenmesini amaçladık. Gereç ve Yöntem: Çalışmamızda 16-26 gebelik haftalarında 125 tekiz gebe, onamı alınarak çalışmaya dahil edildi. Hastalardan 3’ünde karyotip anomalisi (Trizomi 21) saptandı, 1 hastanın gebeliği şiddetli preeklampsi nedeni ile 32. haftada sonlandırıldı, 5 hastaya da ulaşılamadı. 116 hasta ile çalışmaya devam edildi. Amniosentez işlemi alınan ilk 2 cc’lik amniyon mayisi kullanılarak glukoz, IL-1, IL-6, HsCRP, hücre sayımı, elektrolit ve Progesteron/ Estrojen oranı çalışıldı. Bulgular: Gebelerin 16 tanesi 37. haftasını doldurmadan doğum yaptı (%13,8). Çalışma poülasyonunun ortalama yaşı 33,2±6,25 idi. Çalışmamızda preterm doğum yapan grup ile miadında doğum yapan grubun yaş ortalaması istatistiksel olarak benzer bulundu (36,06±3,91 vs 32,77±6,43). Ayrıca her iki grupta hastaların amnion mayisindeki glukoz, IL-1, IL-6, HsCRP, hücre sayımı, elektrolit ve Progesteron/Estrojen oranı istatiksel olarak anlamlı farklı bulunmadı. Sonuç: Çalışmamızda preterm eylemin etyolojisinde suçlanan subklinik enfeksiyon ve steroid hormon değişimleri incelenmiş ve bu hipotezleri destekleyen kanıt bulunamamıştır.

Keywords

• Amniyosentez
• preterm doğum
• glukoz
• nterlökin
• yüksek sensitiviteli C-reaktif protein
• lökosit sayımı

References

1. 1. Amon E. Preterm labor. In: Reece EA, Hobbins JC, Mahoney MJ, Petrie RH, editors. Medicine of the fetus and mothers. Philadelphia: Lippincott-Raven 1999. p.1529-79.
2. 2. Rush RW, Davey DA, Segall ML. The effect of preterm delivery on perinatal mortality. Br J Obstet Gynaecol 1978;85(11):806-11. [CrossRef]
3. 3. Lockwood CJ, Senyei AE, Dische MR, Casal D, Shah KD, Thung SN, et al. Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. N Engl J Med 1991;325(10):669-74. [CrossRef]
4. 4. Bittar RE, Yamasaki AA, Sasaki S, Zugaib M. Cervical fetal fibronectin in patients at increased risk for preterm delivery. Am J Obstet Gynecol 1996;175(1):178-81. [CrossRef]
5. 5. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012;379(9832):2162-72. [CrossRef]
6. 6. Vincer MJ, Allen AC, Joseph KS, Stinson DA, Scott H, Wood E. Increasing prevalence of cerebral palsy among very preterm infants: a population-based study. Pediatrics 2006;118(6):e1621-6. [CrossRef]
7. 7. Iavazzo C, Tassis K, Gourgiotis D, Boutsikou M, Baka S, Hassiakos D, et al. The role of human beta defensins 2 and 3 in the second trimester amniotic fluid in predicting preterm labor and premature rupture of membranes. Arch Gynecol Obstet 2010;281(5):793-9. [CrossRef]
8. 8. Hong SN, Joo BS, Chun S, Kim A, Kim HY. Prediction of preterm delivery using levels of vascular endothelial growth factor and leptin in amniotic fluid from the second trimester. Arch Gynecol Obstet 2015;291(2):265-71. [CrossRef]

9. 9. Melekoglu R, Yilmaz E, Ciftci O, Kafadar YT, Celik E. Associations between second-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α and spontaneous preterm delivery in singleton pregnancies. J Perinat Med 2019;47(3):304-10.
10. 10. Oh KJ, Park KH, Kim SN, Jeong EH, Lee SY, Yoon HY. Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta. Placenta 2011;32(10):732-6. [CrossRef]
11. 11. Park H, Park KH, Kim YM, Kook SY, Jeon SJ, Yoo HN. Plasma inflammatory and immune proteins as predictors of intraamniotic infection and spontaneous preterm delivery in women with preterm labor: a retrospective study. BMC Pregnancy Childbirth 2018;18(1):146. [CrossRef]
12. 12. Virgiliou C, Gika HG, Witting M, Bletsou AA, Athanasiadis A, Zafrakas M, et al. Amniotic Fluid and Maternal Serum Metabolic Signatures in the Second Trimester Associated with Preterm Delivery. J Proteome Res 2017;16(2):898-910. [CrossRef]
13. 13. Erzincan SG, Varol FG, Inan C, Sayin NC. Relationship between second-trimester amniotic fluid levels of Prokineticin-1 and Matrix Metalloproteinase-2 with adverse pregnancy outcome. Placenta 2018;62:25-7. [CrossRef]
14. 14. Ghezzi F, Franchi M, Raio L, Di Naro E, Bossi G, D’Eril GV, et al. Elevated amniotic fluid C-reactive protein at the time of genetic amniocentesis is a marker for preterm delivery. Am J Obstet Gynecol 2002;186(2):268-73. [CrossRef]
15. 15. Ozer KT, Kavak ZN, Gökaslan H, Elter K, Pekin T. Predictive power of maternal serum and amniotic fluid CRP and PAPP-A concentrations at the time of genetic amniocentesis for the preterm delivery. Eur J Obstet Gynecol Reprod Biol 2005;122(2):187-90. [CrossRef]
16. 16. Tarim E, Bağiş T, Kiliçdağ EB, Sezgin N, Yanik F. Are amniotic fluid C-reactive protein and glucose levels, and white blood cell counts at the time of genetic amniocentesis related with preterm delivery? J Perinat Med 2005;33(6):524-9. [CrossRef]
17. 17. Kesrouani A, Chalhoub E, El Rassy E, Germanos M, Khazzaka A, Rizkallah J, et al. Prediction of preterm delivery by second trimester inflammatory biomarkers in the amniotic fluid. Cytokine 2016;85:67-70. [CrossRef]
18. 18. Liu Y, Liu Y, Zhang R, Zhu L, Feng Z. Early- or mid-trimester amniocentesis biomarkers for predicting preterm delivery: a meta-analysis. Ann Med 2017;49(1):1-10. [CrossRef]
19. 19. Kim A, Lee ES, Shin JC, Kim HY. Identification of biomarkers for preterm delivery in mid-trimester amniotic fluid. Placenta 2013;34(10):873-8. [CrossRef]
20. 20. Ozgu-Erdinc AS, Cavkaytar S, Aktulay A, Buyukkagnici U, Erkaya S, Danisman N. Mid-trimester maternal serum and amniotic fluid biomarkers for the prediction of preterm delivery and intrauterine growth retardation. J Obstet Gynaecol Res. 2014;40(6):1540-6. [CrossRef]
21. 21. Uludogan M, Kuyumcuoglu U, Gorgen H, Delikara MN. Amniotic fluid glucose levels in intraamniotic infections. J Perinatol 1995;3(1-2):59-63.
22. 22. Thomakos N, Daskalakis G, Papapanagiotou A, Papantoniou N, Mesogitis S, Antsaklis A. Amniotic fluid interleukin-6 and tumor necrosis factor-alpha at mid-trimester genetic amniocentesis: relationship to intra-amniotic microbial invasion and preterm delivery. Eur J Obstet Gynecol Reprod Biol 2010;148(2):147-51. [CrossRef]
23. 23. Ghidini A, Jenkins CB, Spong CY, Pezzullo JC, Salafia CM, Eglinton GS. Elevated amniotic fluid interleukin-6 levels during the early second trimester are associated with greater risk of subsequent preterm delivery. Am J Reprod Immunol 1997;37(3):227-31. [CrossRef]
24. 24. Wenstrom KD, Andrews WW, Hauth JC, Goldenberg RL, DuBard MB, Cliver SP. Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery. Am J Obstet Gynecol 1998;178(3):546-50. [CrossRef]
25. 25. Alvarez-de-la-Rosa M, Rebollo FJ, Codoceo R, Gonzalez Gonzalez A. Maternal serum interleukin 1, 2, 6, 8 and interleukin-2 receptor levels in preterm labor and delivery. Eur J Obstet Gynecol Reprod Biol 2000;88(1):57-60. [CrossRef]
26. 26. Velez DR, Menon R, Thorsen P, Jiang L, Simhan H, Morgan N, et al. Ethnic differences in interleukin 6 (IL-6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels. Ann Hum Genet 2007;71(Pt 5):586-600. [CrossRef]
27. 27. Haluska GJ, Cook MJ, Novy MJ. Inhibition and augmentation of progesterone production during pregnancy: effects on parturition in rhesus monkeys. Am J Obstet Gynecol 1997;176(3):682-91. [CrossRef]
28. 28. Liggins GC, Fairclough RJ, Grieves SA, Forster CS, Knox BS. Parturition in the sheep. Ciba Found Symp. 1977;(47):5-30. [CrossRef]
29. 29. Kota SK, Gayatri K, Jammula S, Kota SK, Krishna SV, Meher LK, et al. Endocrinology of parturition. Indian J Endocrinol Metab 2013;17(1):50-9. [CrossRef]
30. 30. Davidson BJ, Murray RD, Challis JR, Valenzuela GJ. Estrogen, progesterone, prolactin, prostaglandin E2, prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha gradients across the uterus in women in labor and not in labor. Am J Obstet Gynecol 1987;157(1):54-8. [CrossRef]
31. 31. Yemini M, Borenstein R, Dreazen E, Apelman Z, Mogilner BM, Kessler I, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol 1985;151(5):574-7. [CrossRef]
32. 32. Erny R, Pigne A, Prouvost C, Gamerre M, Malet C, Serment H, et al. The effects of oral administration of progesterone for premature labor. Am J Obstet Gynecol 1986;154(3):525- 9. [CrossRef]
33. 33. Khan-Dawood FS. In vitro conversion of pregnenolone to progesterone in human term placenta and fetal membranes before and after onset of labor. Am J Obstet Gynecol 1987;157(6):1333-7. [CrossRef]
34. 34. Romero R, Scoccia B, Mazor M, Wu YK, Benveniste R. Evidence for a local change in the progesterone/estrogen ratio in human parturition at term. Am J Obstet Gynecol 1988;159(3):657-60. [CrossRef]
35. 35. Mazor M, Wiznitzer A, Levy J, Sharoni Y, Meril Z, Minster A, et al. The relationship between estrogen/progesterone ratio and term human parturition. Isr J Med Sci 1993;29(2-3):97-9.
36. 36. Park KH, Kim SN, Oh KJ, Lee SY, Jeong EH, Ryu A. Noninvasive prediction of intra-amniotic infection and/or inflammation in preterm premature rupture of membranes. Reprod Sci 2012;19(6):658-65.