The assessment of fetal cardiac functions in pregnancies with autoimmune diseases: a prospective case-control study

Muradiye Yildirim; Deniz Oluklu; Dilek Menekse Beser; Derya Uyan Hendem; Betul Akgun Aktas; Esra Gulen Yildiz; Ozgur Kara; Dilek Sahin

doi:10.1515/jpm-2023-0108

Article

The assessment of fetal cardiac functions in pregnancies with autoimmune diseases: a prospective case-control study

Muradiye Yildirim , Deniz Oluklu , Dilek Menekse Beser , Derya Uyan Hendem , Betul Akgun Aktas , Esra Gulen Yildiz , Ozgur Kara and Dilek Sahin

Published/Copyright: August 3, 2023

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From the journal Journal of Perinatal Medicine Volume 51 Issue 8

Abstract

Objectives

This study aimed to assess the effect of the inflammatory process on fetal cardiac functions in pregnant women with autoimmune diseases (AID).

Methods

This prospective study included 36 pregnant women with diagnosed AID. Nineteen systemic lupus erythematosus, 12 antiphospholipid syndrome, 5 Sjögren’s syndrome, and 72 healthy pregnancies were included. Fetal cardiac functions were evaluated with pulsed-wave, tissue Doppler, and M-mode echocardiography.

Results

Sociodemographic data were similar in both groups. Significant increases were found in tricuspid E (43.5 ± 0.9, p<0.001) and A (59.2 ± 2.2, p<0.001) and E/A (0.74 ± 0.03, p<0.001), E’/A’ (0.64 ± 0.15, p<0.001), E/E’ (6.5 ± 0.6, p<0.001), and left ventricular myocardial performance index (0.54 ± 0.03, p=0.005). We demonstrated a significant decrease in tricuspid E’ (6.7 ± 0.6, p<0.001) and S’ (6.9 ± 1, p<0.001) and in TAPSE (7.7 ± 0.5, p=0.002). We also found a significantly prolonged PR interval (130 ± 8, p<0.001). There was a significant increase in E’ (6.8, p=0.033) and a significant decrease in E/E′ ratio (6.4, p=0.027) in the group using hydroxychloroquine (HCQ) compared to non-users.

Conclusions

We found that pregnancy with autoimmune diseases affects fetal heart functions. Additionally, hydroxychloroquine may positively affect the heart of AID fetuses. This information might be useful to clinicians in the follow-up of cardiovascular diseases.

Keywords: antiphospholipid antibody syndrome; fetal cardiac functions; pregnancy; Sjögren’s syndrome; systemic lupus erythematosus; tissue Doppler imaging

Corresponding author: Muradiye Yildirim, MD, Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, 1604th Street, No: 9, Cankaya, Ankara, 06800, Türkiye, Phone: +905052142468, E-mail: my48523@gmail.com

Acknowledgments

We would like to thank all the health personnel.

Research funding: None declared.
Author contributions: All authors contributed to the study’s conception and design. The first draft of the manuscript was written by Muradiye Yıldırım. Material preparation, data collection, and analysis were performed by Muradiye Yıldırım, Deniz Oluklu, Dilek Menekse Beser, and Derya Uyan Hendem, Betul Akgun Aktas, Esra Gulen Yildiz. Literature search and project development were performed by Ozgur Kara. Dilek Sahin contributed to project development, visualization, reviewing, and editing. All authors read and approved the final manuscript.
Competing interests: The authors declare that they have no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors’ Institutional Review Board (E2-22-1385).

References

1. De Luca, F, Shoenfeld, Y. The microbiome in autoimmune diseases. Clin Exp Immunol 2019;195:74–85. https://doi.org/10.1111/cei.13158.Search in Google Scholar PubMed PubMed Central

2. Somers, EC. Pregnancy and autoimmune diseases. Best Pract Res Clin Obstet Gynaecol 2020;64:3–10. https://doi.org/10.1016/j.bpobgyn.2019.11.004.Search in Google Scholar PubMed

3. Bogdanos, DP, Smyk, DS, Rigopoulou, EI, Sakkas, LI, Shoenfeld, Y. Infectomics and autoinfectomics: a tool to study infectious-induced autoimmunity. Lupus 2015;24:364–73. https://doi.org/10.1177/0961203314559088.Search in Google Scholar PubMed

4. Aringer, M, Costenbader, K, Daikh, D, Brinks, R, Mosca, M, Ramsey-Goldman, R, et al.. 2019 European league against rheumatism/American college of rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019;71:1400–12, https://doi.org/10.1002/art.40930.Search in Google Scholar PubMed PubMed Central

5. Negrini, S, Emmi, G, Greco, M, Borro, M, Sardanelli, F, Murdaca, G, et al.. Sjögren’s syndrome: a systemic autoimmune disease. Clin Exp Med 2022;22:9–25. https://doi.org/10.1007/s10238-021-00728-6.Search in Google Scholar PubMed PubMed Central

6. Miyakis, S, Lockshin, MD, Atsumi, T, Branch, DW, Brey, RL, Cervera, R, et al.. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemostasis 2006;4:295–306. https://doi.org/10.1111/j.1538-7836.2006.01753.x.Search in Google Scholar PubMed

7. Pasoto, SG, Adriano de Oliveira Martins, V, Bonfa, E. Sjögren’s syndrome and systemic lupus erythematosus: links and risks. Open Access Rheumatol Res Rev 2019;11:33–45. https://doi.org/10.2147/oarrr.s167783.Search in Google Scholar

8. Franco, JS, Molano-González, N, Rodríguez-Jiménez, M, Acosta-Ampudia, Y, Mantilla, RD, Amaya-Amaya, J, et al.. The coexistence of antiphospholipid syndrome and systemic lupus erythematosus in Colombians. PLoS One 2014;9:e110242. https://doi.org/10.1371/journal.pone.0110242.Search in Google Scholar PubMed PubMed Central

9. Fischer-Betz, R, Specker, C. Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome. Best Pract Res Clin Rheumatol 2017;31:397–414. https://doi.org/10.1016/j.berh.2017.09.011.Search in Google Scholar PubMed

10. Chen, HH, Lin, CH, Chao, WC. Risk of systemic lupus erythematosus in patients with anti-phospholipid syndrome: a population-based study. Front Med 2021;8:654791. https://doi.org/10.3389/fmed.2021.654791.Search in Google Scholar PubMed PubMed Central

11. Merz, WM, Fischer-Betz, R, Hellwig, K, Lamprecht, G, Gembruch, U. Pregnancy and autoimmune disease. Dtsch Arzteblatt Int 2022;119:145–56. https://doi.org/10.3238/arztebl.m2021.0353.Search in Google Scholar PubMed PubMed Central

12. Marder, W, Littlejohn, EA, Somers, EC. Pregnancy and autoimmune connective tissue diseases. Best Pract Res Clin Rheumatol 2016;30:63–80. https://doi.org/10.1016/j.berh.2016.05.002.Search in Google Scholar PubMed PubMed Central

13. Clark, CA, Spitzer, KA, Laskin, CA. Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period. J Rheumatol 2005;32:1709–12.Search in Google Scholar

14. Nalli, C, Iodice, A, Andreoli, L, Lojacono, A, Motta, M, Fazzi, E, et al.. The effects of lupus and antiphospholipid antibody syndrome on foetal outcomes. Lupus 2014;23:507–17. https://doi.org/10.1177/0961203313501402.Search in Google Scholar PubMed

15. Barros, T, Braga, J, Abreu, M, Brandão, M, Farinha, F, Marinho, A, et al.. Sjögren’s syndrome and pregnancy: a Portuguese case-control study. Reumatologia 2022;60:311–7. https://doi.org/10.5114/reum.2022.120754.Search in Google Scholar PubMed PubMed Central

16. Skinner, C, Mount, CA. Sonography assessment of gestational age. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright© 2022, StatPearls Publishing LLC.; 2022.Search in Google Scholar

17. Mahajan, A, Henry, A, Meriki, N, Hernandez-Andrade, E, Crispi, F, Wu, L, et al.. The (Pulsed-Wave) Doppler fetal myocardial performance index: technical challenges, clinical applications and future Research. Fetal Diagn Ther 2015;38:1–13. https://doi.org/10.1159/000363181.Search in Google Scholar PubMed

18. Zanardini, C, D’Antonio, F, Hvingel, B, Vårtun, Å, Prefumo, F, Flacco, ME, et al.. Agreement between anatomical M-mode and tissue Doppler imaging in the assessment of fetal atrioventricular annular plane displacement in uncomplicated pregnancies: a prospective longitudinal study. J Obstet Gynaecol Res 2019;45:2150–7. https://doi.org/10.1111/jog.14068.Search in Google Scholar PubMed

19. Faul, F, Erdfelder, E, Lang, AG, Buchner, AG. *Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007;39:175–91. https://doi.org/10.3758/bf03193146.Search in Google Scholar PubMed

20. Thompson, LP, Turan, S, Aberdeen, GW. Sex differences and the effects of intrauterine hypoxia on growth and in vivo heart function of fetal Guinea pigs. Am J Physiol Regul Integr Comp Physiol 2020;319:R243–54. https://doi.org/10.1152/ajpregu.00249.2019.Search in Google Scholar PubMed PubMed Central

21. Romero, R, Espinoza, J, Gonçalves, LF, Gomez, R, Medina, L, Silva, M, et al.. Fetal cardiac dysfunction in preterm premature rupture of membranes. J Matern Fetal Neonatal Med 2004;16:146–57. https://doi.org/10.1080/jmf.16.3.146.157.Search in Google Scholar

22. Nii, M, Roman, KS, Kingdom, J, Redington, AN, Jaeggi, ET. Assessment of the evolution of normal fetal diastolic function during mid and late gestation by spectral Doppler tissue echocardiography. J Am Soc Echocardiogr 2006;19:1431–7. https://doi.org/10.1016/j.echo.2006.05.027.Search in Google Scholar PubMed

23. Ataalla, WM, Ziada, DH, Gaber, R, Ossman, A, Bayomy, S, Elemary, BR. The impact of total bile acid levels on fetal cardiac function in intrahepatic cholestasis of pregnancy using fetal echocardiography: a tissue Doppler imaging study. J Matern Fetal Neonatal Med 2016;29:1445–50. https://doi.org/10.3109/14767058.2015.1051020.Search in Google Scholar PubMed

24. Takano, M, Nakata, M, Nagasaki, S, Ueyama, R, Morita, M. Assessment of diastolic function of normal fetal heart using dual-gate Doppler. Ultrasound Obstet Gynecol 2018;52:238–42. https://doi.org/10.1002/uog.18821.Search in Google Scholar PubMed

25. Oluklu, D, Menekse Beser, D, Uyan Hendem, D, Yıldırım, M, Lalelı Koc, B, Tanacan, A, et al.. Assessment of fetal cardiac morphology and functional changes in early-onset and late-onset fetal growth restriction. Int J Gynaecol Obstet 2022;161:241–9. https://doi.org/10.1002/ijgo.14602.Search in Google Scholar PubMed

26. Oluklu, D, Kara, O, Turgut, E, Goncu Ayhan, S, Yildirim, M, Sahin, D. Evaluation of fetal cardiac morphology and functions in pregnant women with familial Mediterranean fever. Echocardiography 2022;39:606–11. https://doi.org/10.1111/echo.15336.Search in Google Scholar PubMed

27. Acharya, G, Räsänen, J, Mäkikallio, K, Erkinaro, T, Kavasmaa, T, Haapsamo, M, et al.. Metabolic acidosis decreases fetal myocardial isovolumic velocities in a chronic sheep model of increased placental vascular resistance. Am J Physiol Heart Circ Physiol 2008;294:H498–504. https://doi.org/10.1152/ajpheart.00492.2007.Search in Google Scholar PubMed

28. Martha, JW, Pranata, R, Wibowo, A, Lim, MA. Tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and mortality in COVID-19: a systematic review and meta-analysis. Int J Infect Dis 2021;105:351–6. https://doi.org/10.1016/j.ijid.2021.02.029.Search in Google Scholar PubMed PubMed Central

29. Frangogiannis, NG. Transforming growth factor-β in myocardial disease. Nat Rev Cardiol 2022;19:435–55. https://doi.org/10.1038/s41569-021-00646-w.Search in Google Scholar PubMed

30. Hong, S, Banchereau, R, Maslow, BL, Guerra, MM, Cardenas, J, Baisch, J, et al.. Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy. J Exp Med 2019;216:1154–69. https://doi.org/10.1084/jem.20190185.Search in Google Scholar PubMed PubMed Central

31. van den Hoogen, LL, van Laar, JM. Targeted therapies in systemic sclerosis, myositis, antiphospholipid syndrome, and Sjögren’s syndrome. Best Pract Res Clin Rheumatol 2020;34:101485. https://doi.org/10.1016/j.berh.2020.101485.Search in Google Scholar PubMed

32. Ece, I, Uner, A, Balli, S, Kibar, AE, Oflaz, MB, Kurdoglu, M. The effects of pre-pregnancy obesity on fetal cardiac functions. Pediatr Cardiol 2014;35:838–43. https://doi.org/10.1007/s00246-014-0863-0.Search in Google Scholar PubMed

33. Huang, Y, Yan, X, Zhao, JX, Zhu, MJ, McCormick, RJ, Ford, SP, et al.. Maternal obesity induces fibrosis in fetal myocardium of sheep. Am J Physiol Endocrinol Metabol 2010;299:E968–75. https://doi.org/10.1152/ajpendo.00434.2010.Search in Google Scholar PubMed PubMed Central

34. Peixoto, AB, Bravo-Valenzuela, NJM, Martins, WP, Słodki, M, Mattar, R, Moron, AF, et al.. Impact of type I and type II maternal diabetes mellitus on fetal cardiac function assessment parameters using spectral and tissue Doppler. Int J Cardiovasc Imaging 2020;36:1237–47. https://doi.org/10.1007/s10554-020-01821-9.Search in Google Scholar PubMed

35. Letti Müller, AL, Barrios Pde, M, Kliemann, LM, Valério, EG, Gasnier, R, Magalhães, JA. Tei index to assess fetal cardiac performance in fetuses at risk for fetal inflammatory response syndrome. Ultrasound Obstet Gynecol 2010;36:26–31. https://doi.org/10.1002/uog.7584.Search in Google Scholar PubMed

36. Wojakowski, A, Izbizky, G, Carcano, ME, Aiello, H, Marantz, P, Otaño, L. Fetal Doppler mechanical PR interval: correlation with fetal heart rate, gestational age and fetal sex. Ultrasound Obstet Gynecol 2009;34:538–42. https://doi.org/10.1002/uog.7333.Search in Google Scholar PubMed

37. Mekinian, A, Lachassinne, E, Nicaise-Roland, P, Carbillon, L, Motta, M, Vicaut, E, et al.. European registry of babies born to mothers with antiphospholipid syndrome. Ann Rheum Dis 2013;72:217–22. https://doi.org/10.1136/annrheumdis-2011-201167.Search in Google Scholar PubMed PubMed Central

Received: 2023-03-11

Accepted: 2023-06-24

Published Online: 2023-08-03

Published in Print: 2023-10-26

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Articles in the same Issue

https://doi.org/10.1515/jpm-2023-0108

Keywords for this article

antiphospholipid antibody syndrome; fetal cardiac functions; pregnancy; Sjögren’s syndrome; systemic lupus erythematosus; tissue Doppler imaging