Does Recurrent Pregnancy Loss Have an Inflammatory Background?

Objective: Although several pathophysiological mechanisms is defined in etiology recurrent pregnancy loss, still causes of half of the cases haven’t revealed yet. It is reported that inflammatory processes take place in the etiology of the disease. In our study, we aimed to reveal the relationship between recurrent pregnancy loss with white blood cell count (WBC), C-reactive protein (CRP) and ferritin levels. Methods: We included our study 90 pregnants having recurrent miscarriage history and 101 pregnants without this, totally 191 patients. Maternal and gestational age, height, weight, body mass index (BMI), gravidity, parity, abortion and living children count and WBC, CRP and ferritin levels of these pregnants were evaluated retrospectively. The suitability of quantitative data for normal distribution was tested by Kolmogorov-Smirnov, Shapiro-Wilk test and graphical evaluations. Student's t-test was used for comparing two groups of normally distributed quantitative data, and Mann Whitney U test was used for two-group comparisons of non-normally distributed data Result: According to outcomes, while the age (p= 0.01; p0.05). While WBC levels of the study group was found to be lower (p=0.045, p 0.05) Conclusion: In our study, WBC, CRP and ferritin parameters did not indicate the inflammatory background in recurrent pregnancy loss. We think that further prospective randomized controlled studies are required regarding these parameters.

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  • Ahmed,S.K., Mahmood, N., Almawi, W.Y, 2015. C-reactive protein gene variants associated with recurrent pregnancy loss independent of CRP serum levels: A case-control study. Gene [Internet]. 569:136–140.
  • Amsalem, H., Kwan, M., Hazan, A., Jones, R.L., Whittle, W., John, C.P., Croy, B.A., Lye, S.T., Caroline E., 2020. Identification of a novel neutrophil population: proangiogenic granulocytes in second-trimester human decidua. J Immulugy. 193: 3070–3079.
  • Bas, F.Y. and Tola, E.N., 2018. The role of complete blood inflammation markers in the prediction of spontaneous abortion. J Med Sci. 34: 1381–1385.
  • Best, L.G., Saxena, R., Anderson, C.M., Barnes, M.R., Hakonarson, H., Falcon, G., Martin, C., Castillo, B.A., Karumanchi, A., Keplin, K., Pearson, N., Lamb, F., Bercier, S., Keating, B.J., 2013. two variants of the C-reactive protein gene are associated with risk of pre-eclampsia in an American Indian population. PLoS One.8: e71231 1-10.
  • Carrington, B., Sacks, G., Regan, L., 2005. Recurrent miscarriage: Pathophysiology and outcome. Curr Opin Obstet Gynecol. 17: 591–597.
  • Challis, J.R., Lockwood, C..J, Myatt, L., Norman, J.E., Iii, J.F.S., Petraglia, F., 2009. Inflammation and pregnancy. reproductive sciences. 16: 206–215.
  • Chaouat, G., Bataille, N.L., Dubanchet, S., Zorbas, S., Sandra, O., Martal, J., 2004. Th1 / Th2 paradigm in pregnancy : Paradigm lost ? Int Arch Allergy Immunol. 134: 93–119.
  • Cohen, Y,, Ascher-landsberg, J., Cohen, A., Lessing, J.B., Grisaru, D., 2014. The role of C-reactive protein measurement as a diagnostic aid in early pregnancy. Eur J Obstet Gynecol [Internet]. 176: 64–67.
  • Daglar, H.K., Kirbas, A., Kaya, B., 2016. The value of complete blood count parameters in predicting preterm delivery. Eur Rewiev Med Pharmacol Sci. 20:801–805.
  • Ghaffari, M.A., Sede, S.A., Rashtchizadeh, N., Mohammadzadeh, G., 2014. Association of CRP gene polymorphism with CRP levels and coronary artery disease in type 2 diabetes in Ahvaz , southwest of Iran. Biolmpacts [Internet]. 4: 133–139.
  • Guo, Y., Zhang, N., Zhang, D., Ren, Q., Ganz, T., Nemeth, E., 2019. Iron homeostasis in pregnancy and spontaneous abortion. Am J Hematol. 94:184–188.
  • Kell, D.B. and Pretorius, E., 20014. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 6: 748–773.
  • Kuroda, K., 2019. Impaired endometrial function and unexplained recurrent pregnancy loss. Hypertension Res Pregnancy. 7: 16–21.
  • Laird, S.M., Tuckerman, E.M., Cork, B.A., Linjawi, S., Blakemore, A.I.F., Li, T.C., 2003. A review of immune cells and molecules in women with recurrent miscarriage. Hum Reprod Update. 9: 163–174.
  • Li, T.C., Makris, M., Tomsu, M., Tuckerman, E., Laird, S., 2002. Recurrent miscarriage: Aetiology, management and prognosis. Hum Reprod Update. 8: 463–481.
  • Lohsoonthorn, V. and Qiu ,C.W.M., 2008. Maternal serum C-reactive protein concentrations in early pregnancy and subsequent risk of preterm delivery. Clin Biochem. 40: 330–335.
  • Malek, A., Bersinger, N.A., Santo, S. Di, Mueller, M.D., Sager, R., Schneider, H., 2006. C-reactive protein production in term human placental tissue. Placenta. 27: 619–225.
  • Morales, E., Guerra, S., García-esteban, R., Guxens, M., Alvarez-pedrerol, M., Bustamante, M., Estivill, X., Anto J.M., Sunyer, J., 2011. Maternal C-reactive protein levels in pregnancy are associated with wheezing and lower respiratory tract infections in the offspring. Am J Obstet Gynecol [Internet]. 204: 164.e1-164.e9.
  • Namaste, S.M., Aaron, G.J., Varadhan, R., Peerson, J.M., Suchdev, P.S., 2017. Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 106: 333-347.
  • Panaqiotakos, D.B. , Pitsavos, C., Manics, Y., Polychronopoulo,s E., Chrysohoou, C.A., Stefanadis, C., 2005. Socio-economic status in relation to risk factors associated with cardiocascular disease, in healthy individuals from the ATTICA study. Eur J Cardiovasc Prev Rehabil [Internet]. 12: 68–74.
  • Pei, C.Z., Kim, Y.J., Baek, K.H., 2019. Pathogenetic factors involved in recurrent pregnancy loss from multiple aspects. Obstet Gynecol Sci. 62: 212–223.
  • Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss : a committee opinion., 2013. Fertil Steril. 99: 63.
  • Raghupathy, R., 2001. Pregnancy : success and failure within the Th1 / Th2 / Th3 paradigm. Semin Immunol. 1: 219–227. Regan, L., Braude, P.R., Trembath, P.L., 1989. Influence of past reproductive performance on risk of spontaneous abortion. BMJ. 299: 541–545.
  • Ryan Wessells, K., Peerson, J.M., Brown, K.H., 2019. Within-individual differences in plasma ferritin, retinol-binding protein, and zinc concentrations in relation to inflammation observed during a short-term longitudinal study are similar to between-individual differences observed cross-sectionally. Am J Clin Nutr. 109: 1484–1492.
  • Sarı, N., Üstün, Y.E., Göçmen, A.Y., Çağlayan, E.K., Kara, M., 2016. Recurrent pregnancy loss is associated with increased serum growth differentiation factor 15 and C-reactive protein. J Turk Ger Gynecol Assoc. 17: 21-38.
  • Ticconi, C., Pietropolli, A., Simone, N. Di Piccione, E., Fazleabas, A., 2019. Endometrial immune dysfunction in recurrent pregnancy loss. Int Joıurnal Molacular Sci. 20: 5332–5361.
  • Tjoa, M.L., van Vugt, J.M.G., Go, A.T.J.J., 2003. Elevated C-reactive protein levels during first trimester of pregnancy are indicative of preeclampsia and intrauterine growth restriction. J Reprod Immunol. 59: 29–37.
  • Weghofer, A., Barad, D.H., Darmon, S.K., Kushnir, V.A., Albertini, D.F., Gleicher, N.,2020. Euploid miscarriage is associated with elevated serum C ‑ reactive protein levels in infertile women : a pilot study. Arch Gynecol Obstet [Internet]. 301: 831–836.
  • Wegmann, T.G., Lin, H., Guilbert, L., Mosmann, T.R.,1993. Bidirectional cytokine interactions in the maternal-fetal relationship : is successful pregnancy a Th 2 phenomenon ? Immulogy Today. 14: 5–8.
  • Wood, A.D., Strachan, A.A., Thies, F., Aucott, L.S., Reid, D.M., Hardcastle, A.C., Mvroeidi, A., Simpson, W.G., Duthie, G.G., Mcdonald, H.M., 2014. Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk. Br J Nutr. 112: 1341–1352.
  • Yilmaz, M., Delibas, I.B., Isaoglu, U., Ingec, M., Borekci, B., Ulug, P., 2015. Relationship between mean platelet volume and recurrent miscarriage : a preliminary study. Achives Med Sci. 11: 983–993.
  • Yuan, M., Jordan, F., Mcinnes, I.B., Harnett, M.M., Norman, J.E.,2009. Leukocytes are primed in peripheral blood for activation during term and preterm labour. Mol Hum Reprod. 15:713–724.