Increasing the Prediction Power of Preterm Labor using Interleukin 6 and Fetal Fibronectin as Alarming Signals in Symptomatic Patients

Amal Abdul Muhsen Hussain; Yasamin Hamza Sharif

doi:10.3889/oamjms.2022.8841

Authors

Amal Abdul Muhsen Hussain Department of Obstetrics and Gynecology, Maternity and Pediatric Teaching Hospital, AL-Diwaniyah, Iraq
Yasamin Hamza Sharif Department of Obstetrics and Gynecology, College of Medicine, University of Al-Qadisiyah, Al-Diwaniyah, Iraq

DOI:

https://doi.org/10.3889/oamjms.2022.8841

Keywords:

Cervico-vaginal fluid, Fetal fibronectin, Interleukin 6, Preterm labor

Abstract

Background: Giving birth at preterm is considered as a bothering problem to both healthcare systems and pregnant women around the world, causing alarming levels of mortality. To avoid this issue, certain biological markers can be employed for early detection to predict the occurrence of the PTD (PTD) ahead of time for giving better medical care to the pregnant women who at risk of PTD.

Objective: The current study was performed to evaluate the power of using interleukin-6 (IL-6) and fetal fibronectin (fFN) present in the cervicovaginal fluid (CVF) as predictors of the symptomatic PTD patients.

Patients & Methods: In this study, 91 pregnant hospital attendees (24-34 weeks; 18-45 years old) with suggested PTD symptoms, such as abdominal pain and uterine contraction and with cervical length of less than 25mm, were participated. To detect IL-6 and fFN, vaginal swabs were collected for performing an ELISA test to later follow up with the patients within 48hrs, seven days, and 14 days from the first day of admission to the hospital.

Results: No significant association between PTD with patients age, parity, BMI, and gestational age, but significant association with previous history of PTD. There was significant association between PTD and increase the level of CVF fFN and IL-6 with best cut-off value for CVF fFN is(>45ng/ml) with (95%CI of 0.763-0.918) and accuracy of 85.2% with a sensitivity of 73.1% and specificity of 95.6% which is of high significant value (P≤0.01).While CVF of IL-6 (>231pg/ml) with (95% CI of 0.630- 0.820), with accuracy of 73.3%, sensitivity of 50% and specificity of 96.9% which was statistically significant finding (P≤0.01).The predictive value of combined fFN and IL-6 in women at risk of preterm labor was 84.6% with sensitivity 84.6%,specificity 92.3%, positive predictive value (PPV) 81.5%, negative predictive value (PPV) 93.8% and accuracy of 90.1%.

Conclusion: Each of fFN or IL-6 located in the CVF may provide a strong predictor of PTD; however, this prediction capability may provide an even stronger signal of detecting PTD ahead of time if both biomarkers requested at the same time.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

RomeraR, Dey SK, Fisher SJ. Preterm labor: One syndrome, many causes. Science. 2014;345(6198):760-5. https://doi.org/10.1126/science.1251816 PMid:25124429 DOI: https://doi.org/10.1126/science.1251816

Blencowe H, Cousens S, Oestergaard MZ, Chon D,Moller AB, Narwal R, et al. National, regional, and worldwide estimates of PTD rate in the year 2010 with time trends since 1990 for selected countries: A systemic analysis and implications. Lancet. 2012;379:2162-7. https://doi.org/10.1016/s0140-6736(12)60820-4 DOI: https://doi.org/10.1016/S0140-6736(12)60820-4

Dekker GA, Lee SY, North RA, McCowan LM, Simpson NA, Roberts CT. Risk factors for PTD in an international prospective cohort of nulliparous women. PLoS One. 2012;7(7):e39154. PMid:22815699 DOI: https://doi.org/10.1371/journal.pone.0039154

Corwin EJ. Understanding cytokines part I: Physiology and mechanism of action. Biol Res Nurs. 2000;2(1):30-40. PMid:11232509 DOI: https://doi.org/10.1177/109980040000200104

Coleman MA, Keelan JA, McCowan LM, Townend KM, Mitchell MD. Predicting PTD: Comparison of cervcovaginal interleukin (IL) IB, IL6 and IL8 with fetal fibronectin and cervical dilatation. Eur J Obstet Gynecol Reprod Biol 2001;95(2):154-8. https://doi.org/10.1016/s0301-2115(00)00450-4 PMid:11301160 DOI: https://doi.org/10.1016/S0301-2115(00)00450-4

Foster C, Shennan AH. Fetal fibronectin as a biomarker of preterm labour: A review of literature and advances in its clinical use. Biomark Med. 2014;8(4):471-84. https://doi.org/10.2217/bmm.14.28 PMid:24796611 DOI: https://doi.org/10.2217/bmm.14.28

Lawlor DA, Mortensen L, Andersen AM. Mechanisms underlying the associations of maternal age with adverse perinatal outcomes: A sibling study of 264 695 Danish women and their firstborn offspring. Int J Epidemiol. 2011;40(5):1205-19. https://doi.org/10.1093/ije/dyr084 PMid:21752786 DOI: https://doi.org/10.1093/ije/dyr084

Vinturache A, Moledina N, McDonald S, Slater D and Tough S. Pre-pregnancy Body Mass Index (BMI) and delivery outcomes in a Canadian population. BMC Pregnancy Childbirth. 2014;14:422. https://doi.org/10.1186/s12884-014-0422-y PMid:25528667 DOI: https://doi.org/10.1186/s12884-014-0422-y

Smith GC, Shah I, Pell JP, Crossley JA, Dobbie R. Maternal obesity in early pregnancy and risk of spontaneous and elective preterm deliveries: A retrospective cohort study. Am J Public Health. 2007;97(1):157-62. https://doi.org/10.2105/ajph.2005.074294 PMid:17138924 DOI: https://doi.org/10.2105/AJPH.2005.074294

Cnattingius S, Villamor E, Johansson S, Bonamy AK, Persson M, Wikström AK, et al. Maternal obesity and risk of PTD. JAMA. 2013;309(22):2362-70. https://doi.org/10.1001/jama.2013.6295 PMid:23757084 DOI: https://doi.org/10.1001/jama.2013.6295

Gibbs CM, Wendt A, Peters S, Hogue CJ. The impact of early age at first childbirth on maternal and infant health. Paediatr Perinat Epidemiol. 2012;26(Suppl 1):259-84. https://doi.org/10.1111/j.1365-3016.2012.01290.x PMid:22742615 DOI: https://doi.org/10.1111/j.1365-3016.2012.01290.x

Hendler I, Goldenberg RL, Mercer BM, Iams JD, Meis PJ, Moawad AH, et al. The preterm prediction study: Association between maternal body mass index and spontaneous and indicated PTD. Am J Obstet Gynecol. 2005;192(3):882-891. https://doi.org/10.1016/j.ajog.2004.09.021 PMid:15746686 DOI: https://doi.org/10.1016/j.ajog.2004.09.021

Laughon SK, Albert PS, Leishear K, Mendola P. The NICHD consecutive pregnancies study: Recurrent PTD by subtype. Am J Obstet Gynecol. 2014;210(2):131.e1-8. https://doi.org/10.1016/j.ajog.2013.09.014 PMid:24036403 DOI: https://doi.org/10.1016/j.ajog.2013.09.014

Simonsen SE, Lyon JL, Stanford JB, Porucznik CA, Esplin MS, Varner MW. Risk factors for recurrent PTD in multiparous Utah women: A historical cohort study. BJOG. 2013;120(7):863-872. https://doi.org/10.1111/1471-0528.12182 PMid:23418923 DOI: https://doi.org/10.1111/1471-0528.12182

Kistka ZA, Palomar L, Lee KA, Boslaugh SE, Wangler MF, Cole FS, et al. Racial disparity in the frequency of recurrence of PTD. Am J Obstet Gynecol. 2007;196(2):131.e1-6. https://doi.org/10.1016/j.ajog.2006.06.093 PMid:17306652 DOI: https://doi.org/10.1016/j.ajog.2006.06.093

Peaceman AM, Andrews WW, Thorp JM, Cliver SP, Lukes A, Iams JD, et al. Fetal fibronectin as a predictor of PTD in patients with symptoms: A multicenter trial. Am J Obstet Gynecol. 1997;177(1):13-8. https://doi.org/10.1016/s0002-9378(97)70431-9 PMid:9240576 DOI: https://doi.org/10.1016/S0002-9378(97)70431-9

Greenhagen JB, Van Wagoner J, Dudley D, Hunter C, Mitchell M, Logsdon V, et al. Value of fetal fibronectin as a predictor of PTD for a low-risk population. Am J Obstet Gynecol. 1996;175(4 Pt 1):1054-6. https://doi.org/10.1016/s0002-9378(96)80052-4 PMid:8885775 DOI: https://doi.org/10.1016/S0002-9378(96)80052-4

Berghella V, Saccone G. Fetal fibronectin testing for prevention of PTD in singleton pregnancies with threatened preterm labor: A systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2016;215(4):431-8. https://doi.org/10.1016/j.ajog.2016.04.038 PMid:27133012 DOI: https://doi.org/10.1016/j.ajog.2016.04.038

Woodworth A, Moore J, G’Sell C, Verdoes A, Snyder JA, Morris L, et al. Diagnostic accuracy of cervicovaginal interleukin-6 as markers of PTD. Clin Chem. 2007;53(8):1534-40. https://doi.org/10.1373/clinchem.2007.084798 PMid:17644792 DOI: https://doi.org/10.1373/clinchem.2007.084798

Lockwood CJ, Ghidini A, Wein R, Lapinski R, Casal D, Berkowitz RL. Increased interleukin-6 concentrations in cervical secretions are associated with PTD. Am J Obstet Gynecol. 1994;171(4):1097-102. https://doi.org/10.1016/0002-9378(94)90043-4 PMid:7943078 DOI: https://doi.org/10.1016/0002-9378(94)90043-4

Grenache DG, Hankins K, Parvin CA, Gronowski AM. Cervicovaginal interleukin-6, tumor necrosis factor-α, and interleukin-2 receptor as markers of PTD. Clin Chem. 2004;50(10):1839-42. https://doi.org/10.1373/clinchem.2004.034280 DOI: https://doi.org/10.1373/clinchem.2004.034280

Bolt LA, Chandiramani M, DeGreeff A, Seed PT, Kurtzman J, Shennan AH. The value of combined cervical length measurement and fetal fibronectin testing to predict spontaneous PTD in asymptomatic high-risk women. J Matern Fetal Neonatal Med. 2011;24(7):928-32. https://doi.org/10.3109/14767058.2010.535872 PMid:21190414 DOI: https://doi.org/10.3109/14767058.2010.535872

Schmitz T, Maillard F, Bessard-Bacquaert S, Kayem G, Fulla Y, Cabrol D, et al. Selective use of fetal fibronectin detection after cervical length measurement to predict spontaneous PTD in women with preterm labor. Am J Obstet Gynecol. 2006;194(1):138-143. https://doi.org/10.1016/j.ajog.2005.05.074 PMid:16389023 DOI: https://doi.org/10.1016/j.ajog.2005.05.074