Top

Published in:

10-04-2023 | Systemic Lupus Erythematosus | Maternal-Fetal Medicine

Evaluation of fetal thymus size in maternal autoimmune diseases: systemic lupus erythematosus, Sjögren’s syndrome and antiphospholipid antibody syndrome

Authors: Derya Uyan Hendem, Deniz Oluklu, Dilek Menekse Beser, Muradiye Yildirim, Duygu Tugrul Ersak, Atakan Tanacan, Dilek Sahin

Published in: Archives of Gynecology and Obstetrics | Issue 4/2024

Abstract

Purpose

To investigate the effect of inflammation on the fetal thymus-thoracic ratio (TTR) in pregnant women with systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS) and antiphospholipid antibody syndrome (APS).

Method

This prospective case–control study included 45 pregnant women with SLE, SS, and APS and 90 gestational age-matched healthy pregnant women between 24 and 37 gestational weeks. The ratio of the anteroposterior fetal thymus length to the transverse mediastinal length was calculated as the TTR in the study groups.

Results

Fetal TTR was significantly lower in the case group (p < 0.001). Fetal TTR in the APS group was significantly lower than SS group (p = 006). The patients using hydroxychloroquine (HCQ) had significantly higher fetal TTR compared to patients not using HCQ (p = 0.004). A moderate negative correlation was found between the disease duration and fetal TTR (r = − 0.552, p < 0.001). In predicting admission to the neonatal intensive unit care (NICU), a value of 0.31 was found for the fetal TTR with a sensitivity of 83.3% and a specificity of 69%

Conclusion

Maternal inflammation in pregnancies with autoimmune diseases may affect the intrauterine milieu of the fetus and cause a lower fetal TTR. Additionally, the lower level of fetal TTR may be more effective and beneficial for the clinician if combined with other risk factors in predicting NICU admission.

Geenen V (2021) The thymus and the science of self. Semin Immunol 43(1):5–14

Janssens I, Cools N (2020) Regulating the regulators: is introduction of an antigen-specific approach in regulatory T cells the next step to treat autoimmunity? Cell Immunol 358:104236CrossRefPubMed

Schett G, Smole J, Zimmermann C et al (2002) The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity. Lupus 11(11):704–715CrossRefPubMed

Coss SL, Zhou D, Chua GT et al (2022) The complement system and human autoimmune diseases. J Autoimmun. https://doi.org/10.1016/j.jaut.2022.102979CrossRefPubMed

Schmidt NS, Voss A, Nilsson AC et al (2022) Salivary gland ultrasound is associated with the presence of autoantibodies in patients with Sjögren’s syndrome: A Danish single-centre study. PLoS One 17(12):e0265057CrossRefPubMedPubMedCentral

De Carolis S, Salvi S, Botta A et al (2014) The impact of primary Sjogren’s syndrome on pregnancy outcome: our series and review of the literature. Autoimmun Rev 13(2):103–107CrossRefPubMed

Lima F, Khamashta MA, Buchanan NM et al (1996) A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol 14(2):131–136PubMed

Mor G, Romero R, Aldo PB et al (2005) Is the trophoblast an immune regulator? The role of Toll-like receptors during pregnancy. Crit Rev Immunol 25(5):375–388CrossRefPubMed

Carp HJ, Meroni PL, Shoenfeld Y (2008) Autoantibodies as predictors of pregnancy complications. Rheumatology 47(suppl_3):iii6–iii8PubMed

10.

Papadimitriou E, Boutzios G, Mathioudakis AG et al (2022) Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: a systematic review and meta-analysis. PLoS One 17(7):e0260759CrossRefPubMedPubMedCentral

11.

Robles DT, Jaramillo L, Hornung RL (2006) Neonatal lupus. Dermatol Online J 12(7):25CrossRefPubMed

12.

Lee JYM, Love PE (2023) A simplified approach to evaluating T cell development by flow cytometry. Methods Mol Biol (Clifton, NJ) 2580:131–149CrossRef

13.

Kobayashi T, Takeba Y, Ohta Y et al (2022) Prenatal glucocorticoid administration accelerates the maturation of fetal rat hepatocytes. Mol Biol Rep 49(7):5831–5842CrossRefPubMed

14.

de Felice C, Toti P, Musarò M et al (2008) Early activation of the hypothalamic-pituitary-adrenal-axis in very-low-birth-weight infants with small thymus at birth. J Matern Fetal Med 21(4):251–254CrossRef

15.

Chaoui R, Heling KS, Lopez AS et al (2011) The thymic-thoracic ratio in fetal heart defects: a simple way to identify fetuses at high risk for microdeletion 22q11. Ultrasound Obstet Gynecol 37(4):397–403CrossRefPubMed

16.

Faul F, Erdfelder E, Lang AG et al (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Meth 39(2):175–191CrossRef

17.

Yildirim M, Ipek A, Dauletkazin G et al (2017) Sonographic measurement of the fetal thymus: relationship with maternal obesity. J Clin Ultrasound 45(5):277–281CrossRefPubMed

18.

Borgelt JM, Möllers M, Falkenberg MK et al (2016) Assessment of first-trimester thymus size and correlation with maternal diseases and fetal outcome. Acta Obstet Gynecol Scand 95(2):210–216CrossRefPubMed

19.

Chen T, Liu HX, Yan HY et al (2016) Developmental origins of inflammatory and immune diseases. Mol Hum Reprod 22(8):858–865CrossRefPubMedPubMedCentral

20.

Diepenbruck I, Much CC, Krumbholz A et al (2013) Effect of prenatal steroid treatment on the developing immune system. J Mol Med (Berlin, Germany) 91(11):1293–1302CrossRef

21.

Jones CA, Nisenbaum R, De Souza LR et al (2020) Antenatal corticosteroid administration is associated with decreased growth of the fetal thymus: a prospective cohort study. J Perinatol 40(1):30–38CrossRefPubMed

22.

Meroni PL, Gerosa M, Raschi E et al (2008) Updating on the pathogenic mechanisms 5 of the antiphospholipid antibodies-associated pregnancy loss. Clin Rev Allergy Immunol 34(3):332–337CrossRefPubMed

23.

Caissutti C, Familiari A, Khalil A et al (2018) Small fetal thymus and adverse obstetrical outcome: a systematic review and a meta-analysis. Acta Obstet Gynecol Scand 97(2):111–121CrossRefPubMed

24.

Zych-Krekora K, Grzesiak M, Kaczmarek P et al (2022) Assessment of fetal thymus size and BMI in pregnant women with diabetes. Ginekol Pol. https://doi.org/10.5603/GP.a2022.0020CrossRefPubMed

25.

Story L, Zhang T, Uus A et al (2021) Antenatal thymus volumes in fetuses that delivered <32 weeks’ gestation: an MRI pilot study. Acta Obstet Gynecol Scand 100(6):1040–1050CrossRefPubMed

26.

Gasthaus CL, Schmitz R, Hammer K et al (2019) Influence of maternal HIV infection on fetal thymus size. J Perinat Med 48(1):67–73CrossRefPubMed

27.

Nau TG, de Murcia KO, Möllers M et al (2018) Foetal thymus size in pregnancies after assisted reproductive technologies. Arch Gynecol Obstet 298(2):329–336CrossRefPubMed

28.

GoncuAyhan S, Turgut E, Oluklu D, OzdenTokalioglu E, MenekseBeser D, MoralogluTekin O et al (2022) Influence of Covid-19 infection on fetal thymus size after recovery. J Perinat Med 50(2):139–143CrossRef

29.

Warby AC, Amler S, Jacobi AM et al (2014) Imaging of fetal thymus in pregnant women with rheumatic diseases. J Perinat Med 42(5):635–639CrossRefPubMed

30.

Vargesson N (2015) Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C 105(2):140–156CrossRef

31.

Chambers CD, Johnson DL, Robinson LK et al (2010) Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum 62(5):1494–1503CrossRefPubMedPubMedCentral

32.

Larosa M, Le Guern V, Guettrot-Imbert G et al (2022) Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study. Rheumatology (Oxford) 61(9):3657–3666CrossRefPubMed

33.

Liu J, Zhang L, Tian Y et al (2022) Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome. J Cell Mol Med 26(15):4357–4370CrossRefPubMedPubMedCentral

34.

Izmirly P, Kim M, Friedman DM et al (2020) Hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti-SSA/Ro-positive mothers. Am J Cardiol 76(3):292–302CrossRef

Title: Evaluation of fetal thymus size in maternal autoimmune diseases: systemic lupus erythematosus, Sjögren’s syndrome and antiphospholipid antibody syndrome
Authors: Derya Uyan Hendem
Deniz Oluklu
Dilek Menekse Beser
Muradiye Yildirim
Duygu Tugrul Ersak
Atakan Tanacan
Dilek Sahin
Publication date: 10-04-2023
Publisher: Springer Berlin Heidelberg
Keywords: Systemic Lupus Erythematosus
Hydroxychloroquine
Published in: Archives of Gynecology and Obstetrics / Issue 4/2024
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-023-07035-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Evaluation of fetal thymus size in maternal autoimmune diseases: systemic lupus erythematosus, Sjögren’s syndrome and antiphospholipid antibody syndrome

Abstract

Purpose

Method

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2024

Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment

Maggots in genital prolapse

Depot medroxyprogesterone acetate and breast cancer: a systematic review

Pitfalls in the diagnostics of shoulder dystocia: an analysis based on the scrutiny of 2274 deliveries

Childbirth-associated post-traumatic stress disorders: which matters most, delivery mode, condition severity, or anticipation?

Diagnostic performance of additional imaging tests for staging purposes in a bicentric German series of low-risk early breast cancer patients