C-REACTIVE PROTEIN LEVELS - INDICATOR FOR PROGNOSIS OF SPONTANEOUS PRETERM BIRTH IN BULGARIAN WOMEN
Keywords:CRP, preterm birth, term birth, inflammation
It is estimated that every year fifteen million premature babies are born worldwide mainly due to spontaneous preterm birth (sPTB). Furthermore, in clinical settings, there still are no reliable and accurate tools to predict preterm labor. Hence, the aim of this pioneering research was to estimate the relationship between the maternal inflammatory indicator and sPTB in a case-control study between 220 South Bulgarian women. The study was conducted at UMBAL, Stara Zagora, Bulgaria (2017-2020) and enrolled a total of 220 women, determined into two groups: 1) TB (n = 110), who were to give birth at term ≥ 37 to ≤ 39 + 6 gestation weeks with active labor at the time of hospitalization; and 2) sPTB (n = 110), women with preterm birth ≤ 32–34 + 6 gestation weeks and declared active labor, who were to give birth within 5-24 hrs. The inflammatory indicators/CRP concentration was quantified in plasma by immunoturbidimetric methods within 2 hrs. in mg/l. The median maternal CRP (8.77 ± 3.91), with cutoff = 4.9 mg/l was identified as optimal inflammation with highest risk of sPTB (sensitivity = 86.6%; specificity = 53.7%, р < 0.0001). Moreover, a cutoff CRP = 4.9 mg/l was found to be most effective in determining maternal age ≤ 19 years, the sensitivity of 68.6%, and positively correlated OR = 8.122 vs. OR = 2.354, with increased total sPTB risk at ≤ 32-34 + 6 weeks, respectively (p < 0.001).
In conclusion, increased CRP concentrations and a decreased maternal age were associated with increased risks of sPTB, before ≤ 32-34 + 6 weeks. Minimal inflammation and other factors in combination may also act as sPTB prognosis.
Almskaar, K. (2019). The Placental Microbiome and Preterm Birth: An Evolutionary Life History Perspective (Doctoral dissertation), Libraries. Temple University.
Catov, J. M., Bodnar, L. M., Ness, R. B., Barron, S. J., & Roberts, J. M. (2007). Inflammation and dyslipidemia related to risk of spontaneous preterm birth. American journal of epidemiology, 166 (11), 1312-1319.
Catov, J. M., Bodnar, L. M., Ness, R. B., Barron, S. J., & Roberts, J. M. (2008). Inflammation and Dyslipidemia Related to Risk of Spontaneous Preterm Birth. Obstetrical & Gynecological Survey, 63 (4), 213.
Cetinkaya, S., Ozaksit, G., Biberoglu, E. H., Oskovi, A., Kirbas, A. (2017). The value of acute phase reactants in predicting preterm delivery. J Matern fetal Neonatal Med. 30 (24): 3004–8.
Di Tommaso, M., & Berghella, V. (2013). Cervical length for the prediction and prevention of preterm birth. Expert Review of Obstetrics & Gynecology, 8 (4), 345-355.
Diamanti-Kandarakis, E., Papalou, O., Kandaraki, E. A., & Kassi, G. (2017). Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women. Eur. J. Endocrinol., 176, R79-R99.
Dodds, W. G., Lams, J. D. (2003). Maternal C-reactive protein and preterm labor. J Repord Med.; 32: 527-530.
D'Silva, A. M. (2018). Identification of first trimester maternal serum markers predictive of spontaneous preterm birth. Western Sydney University, Australia.
Esplin, M. S. (2014). Overview of spontaneous preterm birth: a complex and multifactorial phenotype. Clinical obstetrics and gynecology, 57 (3), 518-530.
Ferguson, K. K., McElrath, T. F., Chen, Y. H., Mukherjee, B., & Meeker, J. D. (2014). Longitudinal profiling of inflammatory cytokines and C‐reactive protein during uncomplicated and preterm pregnancy. American journal of reproductive immunology, 72 (3), 326-336.
Guney, G., Taskin, M. I., & Tokmak, A. (2020). Increase of circulating inflammatory molecules in preeclampsia, an update. European Cytokine Network, 31, 18-31.
Hendler, I., Goldenberg, R. L., Mercer, B. M., et al. (2005). The Preterm Prediction study: association between maternal body mass index and spontaneous and indicated preterm birth, Am J Obstet Gynecol, vol. 192, pp. 882-6.
Ho, M., Faye-Petersen, O. M., Goldenberg, R. L., Carlo, W. A., Cliver, S. P., & Andrews, W. W. (2012). Elevated midtrimester α-fetoprotein and delivery markers of inflammation in a preterm population. The Journal of Maternal-Fetal & Neonatal Medicine, 25 (11), 2424-2427.
Huang, S., Tian, J., Liu, C., Long, Y., Cao, D., Wei, L., Zhu, X., Tang, R., Liu, W., Zeng, D. and Li, M. (2020). Elevated C-reactive protein and complement C3 levels are associated with preterm birth: a nested case–control study in Chinese women. BMC pregnancy and childbirth, 20 (1), 1-9.
Lamont, R. F. (2015). Advances in the prevention of infection-related preterm birth. Frontiers in immunology, 6, 566.
Lamont, R. F. (2019). Spontaneous preterm labour that leads to preterm birth: An update and personal reflection. Placenta, 79, 21-29.
Lashen, H., Fear, K., & Sturdee, D. W. (2004). Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case–control study. Human reproduction, 19 (7), 1644-1646.
Liggins, G. C. (1981). Cervical ripening as an inflammatory reaction. The cervix in pregnancy and labor. Clinical and biochemical investigation, 1-9.
Lucaroni, F., Morciano, L., Rizzo, G., D’Antonio, F., Buonuomo, E., Palombi, L., & Arduini, D. (2018). Biomarkers for predicting spontaneous preterm birth: an umbrella systematic review. The Journal of Maternal-Fetal & Neonatal Medicine, 31 (6), 726-734.
Menon, R. (2008). Spontaneous preterm birth, a clinical dilemma: etiologic, pathophysiologic and genetic heterogeneities and racial disparity. Acta obstetricia et gynecologica Scandinavica, 87 (6), 590-600.
Menon, R. (2019). Initiation of human parturition: signaling from senescent fetal tissues via extracellular vesicle mediated paracrine mechanism. Obstetrics & gynecology science, 62 (4), 199.
Mitchell, M. D., Rice, G. E., Vaswani, K., Kvaskoff, D., & Peiris, H. N. (2016). Differential regulation of eicosanoid and endocannabinoid production by inflammatory mediators in human choriodecidua. PloS one, 11 (2), e0148306.
Moghaddam Banaem, L., Mohamadi, B., Asghari Jaafarabadi, M., & Aliyan Moghadam, N. (2012). Maternal serum C‐reactive protein in early pregnancy and occurrence of preterm premature rupture of membranes and preterm birth. Journal of Obstetrics and Gynaecology Research, 38 (5), 780-786.
Nakishbandy, B. M. N., & Barawi, S. A. (2014). Level of C-reactive protein as an indicator for prognosis of premature uterine contractions. Journal of prenatal medicine, 8 (1-2), 25.
Navolan, D. B., Stoian, D. L., Bohiltea, R. E., Crainiceanu, Z., Craina, M. L., Cretu, O., Timar, B., Vladareanu, R., Terness, P., Būrger, F. andNemescu, D. (2020). Comparison of early pregnancy serum concentration of neopterin, neopterin/creatinine ratio, C‑reactive protein, and chitotriosidase, in pregnant women with birth at term and spontaneous preterm birth. Experimental and Therapeutic Medicine, 20 (3), 2449-2454.
Pitiphat, W., Gillman, M. W., Joshipura, K. J., Williams, P. L., Douglass, C. W., & Rich-Edwards, J. W. (2005). Plasma C-reactive protein in early pregnancy and preterm delivery. American journal of epidemiology, 162(11), 1108-1113.
Rogers, L. K., & Velten, M. (2011). Maternal inflammation, growth retardation, and preterm birth: insights into adult cardiovascular disease. Life Sci., 89 (13-14): 417-21.
Romero, R., Miranda, J., Chaemsaithong, P., Chaiworapongsa, T., Kusanovic, J. P., Dong, Z., Ahmed, A.I., Shaman, M., Lannaman, K., Yoon, B.H. and Kim, Y. M. (2015). Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. The Journal of Maternal-Fetal & Neonatal Medicine, 28 (12), 1394-1409.
Ryu, H. K., Moon, J. H., Heo, H. J., Kim, J. W., & Kim, Y. H. (2017). Maternal c‐reactive protein and oxidative stress markers as predictors of delivery latency in patients experiencing preterm premature rupture of membranes. International Journal of Gynecology & Obstetrics, 136 (2), 145-150.
Seferovic, M. D., Pace, R. M., Carroll, M., Belfort, B., Major, A. M., Chu, D. M., Racusin, D.A., Castro, E.C., Muldrew, K.L., Versalovic, J. andAagaard, K. M. (2019). Visualization of microbes by 16S in situ hybridization in term and preterm placentas without intraamniotic infection. American journal of obstetrics and gynecology, 221 (2), 146-e1.
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