Reinterpreting potential biomarker in umbilical cord as a marker of chorioamnionitis and funisitis in prelabor ROM
Downloads
HIGHLIGHTS
- HsCRP and IL-6 levels in umbilical cord blood serve as reliable early biomarkers of chorioamnionitis and funisitis in prelabor ROM, enabling more accurate neonatal sepsis risk assessment and targeted clinical intervention.
- Early identification of amnionitis and funisitis through hsCRP and IL-6 measurements guides timely clinical decisions, including prompt antibiotics or intensified monitoring, thereby reducing severe neonatal complications.
ABSTRACT
Objective: Prelabor rupture of membranes (ROM) occurs in approximately 1% of all pregnancies and 30% of all preterm births, and the etiology remains unclear. Prelabor ROM is associated with a high incidence of funisitis and chorioamnionitis leading to neonatal sepsis. This study aimed to assess whether hsCRP, procalcitonin, and IL-6 level in umbilical cord as indicators for identifying pregnancies at risk for these complications.
Materials and Methods: This research used cross sectional design conducted in dr.Kariadi hospital. Inclusion criteria were pregnant woman with 28-42 weeks of gestational age, singleton and prelabor ROM. Exclusion criteria included other comorbidities. The participants were divided into two groups: with and without funisitis-chorioamnionitis, which were detected using histopathologic examination. Statistical analysis was performed using the chi-square, t-test/Mann-Whitney between two group, wit statistically significant set at p<0.05.
Results: A total of 88 pregnant women were included in the study, consisting of 23 pregnant women with chorioamnionitis-funisitis and 65 pregnant women without funisitis-chorioamnionitis. Procalcitonin levels in the group with and without chorioamnionitis-funisitis were 0.88±0.6 vs 1.06±0.46 ug/mL (p=0.07). IL-6 levels in the chorioamnionitis-funisitis were 54.41(9.34-445.9) vs 2.83(0.09-454.82) pg/mL in without chorioamnionitis-funisitis (p<0.001). HsCRP levels in the funisitis-chorioamnionitis compared to those without chorioamnionitis-funisitis group were 1.39(0.07-10.5) vs 0.17(0.03-10.5) mg/L (p<0.001).
Conclusion: Elevated levels of hsCRP and IL-6 in the umbilical cord were found to be significant biomarkers for chorioamnionitis and funisitis in prelabor rupture of membranes. These biomarkers could be useful in identifying pregnant women at high risk for these complications, enabling better clinical management.
Cunningham, F.G., Leveno, K.J., Bloom, S.L., Spong, C.Y., Dashe, J.S., Hoffman, B.L., et al. Preterm Premature Rupture of Membranes. In: Williams Obstetrics, 25th ed. McGraw-Hill Education; 2018. p. 819-824.
ACOG. Premature Rupture of Membranes. Practice Bulletin No. 217. American College of Obstetricians and Gynecologists. 2020.
Dulay AT, Buhimschi IA, Zhao G, Bahtiyar MO, Thung SF, Cackovic M et al. Compartmentalization of acute phase reactans interleukin-6, C-reactive protein and procalcitonin as a biomarker of intra-amniotic infection an dchorioamnionitis. Cytokine 2025;76(2):236-43.
Horinaochi T, Yoshizato T, Kozuma Y, Shinagawa T, Muto M, Yamasaki T et al. Prediction of histological chorioamnionitis and neonatal and infantile outcomes using procalcitonin in the umbilical cord blood and amniotic fluid at birth. J Obstet Gyneacol Res 2018;44(4):630-6.
Jain VG, Willis KA, Jobe A, Ambalayanan N. Chorioamnionitis and neonatal outcomes. Pediatr Res 2021;91(2):289-96.
Mithal LB, Becker ME, Hu TL, Ah Goo Y, Otero S, Kremes A et al. Cord blood proteomics identifies biomarkes of early-onset neonatal sepsis. JCI insight 2025;10(13):e193826
Nguyen TTB, Thi DAT, Truong QV, Pham TN. The diagnostic accuracy of umbilical cord procalcitonin early-onset neonatal infection. PLOS ONE 2025;20(1):e0316987
Yuan J, Wu Y, Zhang Y, Zeng L, Zhou J, Piano M et al. Diagnostic value of umbilical cord blood interleukin-6 level in premature infants with early onset sepsis. Children (Basel) 2025;12(3):301
Diaz NM, Zemtsov GE, Ryan E, Choo A, Santali CMA, Grace MR. Maternal and peripartum risk factors for acute funisitis among term deliveries complicated by intraamniotic infection. American J Obstet and Gynecol 2023;5(8):101013.
Kaambo E, Africa C, Chambuso R, Passmore JS. Vaginal microbiomes associated with aerobic vaginitis and bacterial vaginosis. Frontiers in public health 2018;6:78
Nakubulwa S., Kaye D., Bwanga F., NM N.T., Mirembe F. Genital infections and risk of premature rupture of membranes in Mulago Hospital, Uganda: a case control study. BMC Res Notes. 2015 Oct 16(8):573.
Kyozuka A, Murata T, Fukuda T, Suzuki E, Yazawa R, Yasuda S et al. Labor dystocia and risk of histological chorioamnionitis and funisitis: a study from a single tertiary referral centre. BMC Pregnancy and childbirth 2021;21:263.
Khan N, Khatak S. Frequency of maternal anemia in patients presenting with preterm premature rupture of membrane. Cureus 2024;16(1):e52973.
Jung E, Romero R, Yeo L, Primera RD, Concha JM, Para R et al. The fetal inflammatory response syndrome: the origin of a concept, pathophysiology, diagnosis and obstetrical implications. Seminars in fetal & neonatal medicine 2020;25(4):101146.
Huetz N, Launay E, Gazcoin G, Leboucher B, Savagner C, Muller JB. Potential impact of umbilical cord procalcitonin based algortithm on antibiotics exposure in neonates with suspected early onset sepsis. Front Pediatr 2020;17(8):127.
Pasquo ED, Fieni S, Chandraharan E, Golli L, Perrone S, Ghi T et al. Correlation between intrapartum CTG findings and interleukin-6 levels in the umbilical cord arterial blood: A prospective cohort study. Eur J Obstet and Gynecol 2024;294:128-34.
Samejima T, Takechi K. Elevated C-reactive protein levels in histological chorioamnionitis at term: impact of funisitis on term neonates. J Matern Fetal Neonatal Med 2017;30(12):1428-33.
Tissieres P, Torne EE, Hubner J, Randolph A, Galan CR, Weiss SL. Use of procalcitonin in therapeutic decisions in ther pediatric intensive care unit. Annals of intensive care 2025;15:55.
Rashwan NI, Hassan MH, El-Deen ZMM, Abd Ahmed AE. Validity of biomarkers in screening for neonatal sepsis-A single center hospital based study 2019;50(2):149-55.
Abdollahi A, Shoar S, Nayyeri F, Shariat M. Diagnostic value of simultaneous measurement of procalcitonin, interleukin-6 and hs-CRP in prediction of early onset neonatal sepsis. Mediterr J Hematol Infects Dis 2012;4(1):e2012028.
Copyright (c) 2025 Julian Dewantiningrum, Besari Adi Pramono, Agoes Oerip Poerwoko, Budi Irawan, Rizky Aditya Bachrudin, Herman Kristanto

This work is licensed under a Creative Commons Attribution 4.0 International License.
1. Copyright of the article is transferred to the journal, by the knowledge of the author, whilst the moral right of the publication belongs to the author.
2. The legal formal aspect of journal publication accessibility refers to Creative Commons Attribution-Non Commercial-Share alike (CC BY-NC-SA), (https://creativecommons.org/licenses/by-nc-sa/4.0/)
3. The articles published in the journal are open access and can be used for non-commercial purposes. Other than the aims mentioned above, the editorial board is not responsible for copyright violation
The manuscript authentic and copyright statement submission can be downloaded ON THIS FORM.



















