Fetal thymic-thoracic ratio in pregnancies with familial Mediterranean fever

Published:January 22, 2023DOI:



      To investigate the thymic-thoracic ratio (TTR) in fetuses of pregnant women with familial Mediterranean fever (FMF).

      Study design

      This prospective case-control study was conducted with 43 pregnant women diagnosed with FMF and 43 gestational age-matched healthy controls. Pregnant women between 28 and 40 weeks who applied for antenatal care were included in the study. Healthy pregnant women whose age and gestational week matched were defined as the control group.


      TTR was significantly lower in the FMF group compared to the control group. The mean TTR value was 0.34 ± 0.03 in the FMF group and 0.36 ± 0.02 in the control group (p < 0.001). TTR was significantly lower in those with FMF duration of ten years or more than those with FMF of less than ten years (p < 0.001). In addition, pregnant women who had an attack during pregnancy had lower TTR (p < 0.001). TTR was significantly associated with white blood cell count, neutrophil count, monocyte count, platelet count, mean platelet volume, C-reactive protein, red cell distribution width, and platelet‑to‑lymphocyte ratio.


      Besides the inflammation during the FMF attacks, the ongoing subclinical inflammation between the attacks might affect the fetal thymus size. Since TTR is an easily applicable method, it can be used to evaluate fetal inflammation.


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        • Ozdogan H.
        • Ugurlu S.
        Familial mediterranean fever.
        Presse Med. 2019; 48: e61-e76
        • Ben-Chetrit E.
        • Touitou I.
        Familial mediterranean Fever in the world.
        Arthritis Rheum. 2009; 61: 1447-1453
      1. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell. 1997;90(4):797–807.

      2. Shohat M. Familial Mediterranean Fever. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews(®). Seattle (WA): University of Washington, Seattle Copyright © 1993-2023, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.

        • Ben-Zvi I.
        • Livneh A.
        Chronic inflammation in FMF: markers, risk factors, outcomes and therapy.
        Nat Rev Rheumatol. 2011; 7: 105-112
        • Ben-Chetrit E.
        • Levy M.
        Reproductive system in familial Mediterranean fever: an overview.
        Ann Rheum Dis. 2003; 62: 916-919
        • Özer S.
        • Yılmaz R.
        • Sönmezgöz E.
        • Karaaslan E.
        • Taşkın S.
        • Bütün İ.
        • et al.
        Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever.
        Med Sci Monit. 2015; 21: 298-303
        • Ygberg S.
        • Nilsson A.
        The developing immune system – from foetus to toddler.
        Acta Paediatr. 2012; 101: 120-127
        • Gordon J.
        • Manley N.R.
        Mechanisms of thymus organogenesis and morphogenesis.
        Development. 2011; 138: 3865-3878
        • Volpe P.
        • Marasini M.
        • Caruso G.
        • Marzullo A.
        • Buonadonna A.L.
        • Arciprete P.
        • et al.
        22q11 deletions in fetuses with malformations of the outflow tracts or interruption of the aortic arch: impact of additional ultrasound signs.
        Prenat Diagn. 2003; 23: 752-757
        • Cromi A.
        • Ghezzi F.
        • Raffaelli R.
        • Bergamini V.
        • Siesto G.
        • Bolis P.
        Ultrasonographic measurement of thymus size in IUGR fetuses: a marker of the fetal immunoendocrine response to malnutrition.
        Ultrasound Obstet Gynecol. 2009; 33: 421-426
        • Mohamed N.
        • Eviston D.P.
        • Quinton A.E.
        • Benzie R.J.
        • Kirby A.C.
        • Peek M.J.
        • et al.
        Smaller fetal thymuses in pre-eclampsia: a prospective cross-sectional study.
        Ultrasound Obstet Gynecol. 2011; 37: 410-415
        • Sciaky-Tamir Y.
        • Hershkovitz R.
        • Mazor M.
        • Shelef I.
        • Erez O.
        The use of imaging technology in the assessment of the fetal inflammatory response syndrome-imaging of the fetal thymus.
        Prenat Diagn. 2015; 35: 413-419
        • Faul F.
        • Erdfelder E.
        • Lang A.G.
        • Buchner A.
        G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences.
        Behav Res Methods. 2007; 39: 175-191
        • Nabil H.
        • Zayed A.
        • State O.
        • Badawy A.
        Pregnancy outcome in women with familial Mediterranean fever.
        J Obstet Gynaecol. 2012; 32: 756-759
        • Dörnemann R.
        • Koch R.
        • Möllmann U.
        • Falkenberg M.K.
        • Möllers M.
        • Klockenbusch W.
        • et al.
        Fetal thymus size in pregnant women with diabetic diseases.
        J Perinat Med. 2017; 45: 595-601
        • De Leon-Luis J.
        • Gámez F.
        • Pintado P.
        • Antolin E.
        • Pérez R.
        • Ortiz-Quintana L.
        • et al.
        Sonographic measurements of the thymus in male and female fetuses.
        J Ultrasound Med. 2009; 28: 43-48
        • Chaoui R.
        • Heling K.S.
        • Lopez A.S.
        • Thiel G.
        • Karl K.
        The thymic-thoracic ratio in fetal heart defects: a simple way to identify fetuses at high risk for microdeletion 22q11.
        Ultrasound Obstet Gynecol. 2011; 37: 397-403
        • Karl K.
        • Heling K.S.
        • Sarut Lopez A.
        • Thiel G.
        • Chaoui R.
        Thymic-thoracic ratio in fetuses with trisomy 21, 18 or 13.
        Ultrasound Obstet Gynecol. 2012; 40: 412-417
        • Pearse G.
        Histopathology of the thymus.
        Toxicol Pathol. 2006; 34: 515-547
        • De Felice C.
        • Toti P.
        • Santopietro R.
        • Stumpo M.
        • Pecciarini L.
        • Bagnoli F.
        Small thymus in very low birth weight infants born to mothers with subclinical chorioamnionitis.
        J Pediatr. 1999; 135: 384-386
      3. Goncu Ayhan S, Turgut E, Oluklu D, Ozden Tokalioglu E, Menekse Beser D, Moraloglu Tekin O, et al. Influence of Covid-19 infection on fetal thymus size after recovery. J Perinat Med. 2022;50(2):139-43.

        • Goncu Ayhan S.
        • Oluklu D.
        • Sinaci S.
        • Atalay A.
        • Erol S.A.
        • Ozden Tokalioglu E.
        • et al.
        Fetal thymus size in pregnant women with COVID-19 infection.
        Gynecol Obstetr Reprod Med. 2021; 27: 84-88
        • Warby A.-C.
        • Amler S.
        • Jacobi A.M.
        • Hammer K.
        • Möllmann U.
        • Falkenberg M.K.
        • et al.
        Imaging of fetal thymus in pregnant women with rheumatic diseases.
        J Perinat Med. 2014; 42
        • Aydin O.
        • Ugurlu S.
        • Ozdogan H.
        THU0590 comparison of FMF patients with age of onset before 20 versus 40 years and over.
        BMJ Publishing Group Ltd, 2019
      4. Lachmann H, Şengül B, Yavuzşen T, Booth D, Booth S, Bybee A, et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology. 2006;45(6):746–50.

        • Guzel S.
        • Andican G.
        • Seven A.
        • Aslan M.
        • Bolayirli M.
        • Guzel E.C.
        • et al.
        Acute phase response and oxidative stress status in familial Mediterranean fever (FMF).
        Mod Rheumatol. 2012; 22: 431-437