Subclinical intrauterine inflammation as a determinant of extremely early preterm birth: integrated analysis of systemic biomarkers. original study
DOI:
https://doi.org/10.15574/PP.2025.3(103).9298Keywords:
pregnancy, preterm birth, subclinical chorioamnionitis, C-reactive protein, GroEL, cortisol, leukocytosis, Edinburgh Postnatal Depression Scale, interleukin-6, procalcitonin, predictionAbstract
Aim - to determine the predictive value of integrating clinical, laboratory, ultrasound and psychometric markers for assessing the risk of extremely early preterm birth (EEPB) associated with intrauterine infection.
Materials and methods. A prospective cohort study included 223 pregnant women at 22-28 weeks’ gestation, of whom 130 were assigned to the risk group (clinical signs of threatened preterm birth) and 93 to the control group. Systemic inflammatory markers (C-reactive protein, leukocyte count, interleukin-6, procalcitonin), bacterial stress proteins (HSP60, GroEL), cortisol levels, psychometric status (Edinburgh Postnatal Depression Scale ≥13), and transvaginal cervical length were analyzed. A nine-factor predictive model was developed and evaluated using ROC analysis.
Results. The most significant predictors of EEPB included short cervical length (≤25 mm), elevated C-reactive protein (>10 mg/L), increased interleukin-6 (>2 pg/mL), procalcitonin (≥0.046 ng/mL), high GroEL levels (254.99±106.78 ng/mL), hypercortisolemia (6.17±3.64 µg/dL), leukocytosis (>11×10⁹/L), and Edinburgh score ≥13. The integrated model demonstrated an AUC of 0.80, sensitivity of 78.9%, and specificity of 76.3%.
Conclusions. Integration of systemic inflammatory, bacterial, hormonal, and psychometric indicators provides high predictive accuracy for subclinical intrauterine inflammation and EEPB. The availability and reproducibility of these biomarkers make the proposed model applicable to routine practice in perinatal care settings.
This study was conducted in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution involved. Informed consent was obtained from all participants.
The authors declare no conflicts of interest.
References
Chaemsaithong P, Romero R, Korzeniewski SJ et al. (2015). A point-of-care test for interleukin-6 in amniotic fluid to diagnose acute intra-amniotic inflammation. Am J Obstet Gynecol. 213(1): 71.e1-71.e12.
Commissariat M, Baker PN, Roberts CT. (2021). Heat shock proteins (HSP60/HSP70) as potential biomarkers of pregnancy complications. Placenta. 104: 164-171.
Cousens S, Blencowe H, Stanton C et al. (2012). National, regional and worldwide estimates of preterm birth. Lancet. 379(9832): 2162-2172. https://doi.org/10.1016/S0140-6736(12)60820-4; PMid:22682464
Esplin MS, Elovitz MA, Iams JD et al. (2017). Prediction of preterm birth. Obstet Gynecol. 129(5): 947-955.
Fortner KB, Grotegut CA, Richey SD et al. (2012). Maternal serum interleukin-6 levels and risk of preterm birth. Am J Obstet Gynecol. 206(3): e1-e8.
Goldenberg RL, Culhane JF, Iams JD, Romero R. (2008). Epidemiology and causes of preterm birth. Lancet. 371(9606): 75-84. https://doi.org/10.1016/S0140-6736(08)60074-4; PMid:18177778
Gomez R, Romero R, Ghezzi F et al. (1998). The fetal inflammatory response syndrome. Am J Obstet Gynecol. 179(1): 194-202. https://doi.org/10.1016/S0002-9378(98)70272-8; PMid:9704787
Helmo FR, Alves EA, Moreira RA et al. (2018). Intrauterine infection, inflammation, and preterm birth. J Infect Dev Ctries. 12(3): 104-110.
Kacerovsky M, Musilova I, Hornychova H et al. (2014). Preterm prelabor rupture of membranes: infection, inflammation and neonatal outcome. Am J Obstet Gynecol. 210(4): 325.e1-325.e10. https://doi.org/10.1016/j.ajog.2013.10.882; PMid:24184182
McElrath TF, Hecht JL, Dammann O et al. (2008). Pregnancy disorders that lead to delivery before 28 weeks of gestation: a multicenter study. Am J Epidemiol. 167(7): 874-884.
Menon R, Fortunato SJ. (2004). The role of matrix metalloproteinases in preterm prelabor rupture of membranes. Reprod Biol Endocrinol. 2: 70.
Menon R, Mesiano S. (2017). Programmed membrane rupture and PTB: The role of oxidative stress. Am J Obstet Gynecol. 216(6): 497-509.
Muglia LJ, Katz M. (2010). The enigma of spontaneous preterm birth. N Engl J Med. 362(6): 529-535. https://doi.org/10.1056/NEJMra0904308; PMid:20147718
Romero R, Chaemsaithong P, Docheva N et al. (2015). The relationship between microbial invasion of the amniotic cavity and amniotic fluid biomarkers. J Matern Fetal Neonatal Med. 28(12): 1-16.
Romero R, Chaiworapongsa T, Savasan ZA et al. (2014). Evidence of chronic intra-amniotic inflammation in preterm premature rupture of membranes. Am J Obstet Gynecol. 211: 144.e1-144.e16.
Romero R, Espinoza J, Gonçalves LF et al. (2006). Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 11(5): 317-326. https://doi.org/10.1016/j.siny.2006.05.001; PMid:16839830 PMCid:PMC8315239
Romero R, Miranda J, Chaiworapongsa T et al. (2014). A novel molecular microbiologic technique for the diagnosis of microbial invasion of the amniotic cavity. Am J Reprod Immunol. 71(4): 330-358. https://doi.org/10.1111/aji.12189; PMid:24417618 PMCid:PMC3954440
Saccone G, Berghella V. (2019). Cervical length screening for preventing preterm birth. Curr Opin Obstet Gynecol. 31(5): 306-312. https://doi.org/10.1002/14651858.CD007235.pub4; PMid:31553800
Shynlova O, Lee YH, Srikhajon K, Lye S. (2013). Physiologic uterine inflammation and labour. Nat Rev Endocrinol. 9(6): 391-405.
Tsiartas P, Kacerovsky M, Musilova I et al. (2014). Maternal serum C-reactive protein and interleukin-6 levels as predictors of intra-amniotic inflammation. J Matern Fetal Neonatal Med. 27(18): 1821-1828.
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