Metabolic dysfunction-associated steatotic liver disease and adverse pregnancy outcomes: a nationwide cohort study (original) (raw)

Abstract

Purpose

A recent international consensus introduced revised nomenclature for steatotic liver disease (SLD). This study evaluated the impact of SLD subtypes on adverse pregnancy outcomes (apos) using updated criteria.

Methods

In this nationwide, population-based study, we analyzed 290,527 female who underwent health check-ups within 1 year before pregnancy and delivered singleton infants. Participants were categorized into non-SLD, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD) groups.

Results

A total of 290,527 female were analyzed. Compared to female without SLD, those with MASLD (adjusted odds ratio [aOR] 2.44, 95% CI 2.33–2.55), MetALD (aOR 2.45, 95% CI 2.26–2.66) and ALD (aOR 2.28, 95% CI 2.11–2.47) had significantly higher risks of apos. These associations were observed for gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth. Both MASLD and ALD were associated with increased risk of low birthweight (aOR 1.15, 95% CI 1.05–1.27 and aOR 1.21, 95% CI 1.02–1.43, respectively), whereas MetALD was not (aOR 0.96, 95% CI 0.79–1.18). Due to the low incidence of placental abruption across all groups (0.3–0.5%), associations with this outcome remained inconclusive. Additionally, a higher number of cardiometabolic risk factors (CMRFs) was associated with an increased risk of apos (p for trend of odds < 0.0001).

Conclusion

MASLD, MetALD, and ALD were independently associated with increased risks of apos, with risk further amplified by a greater number of CMRFs. These findings underscore the importance of enhanced prenatal management for female with pre-existing SLD, particularly those with multiple CMRFs, to mitigate the risk of apos.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Data availability

The data used in this study are derived from the National Health Insurance Service (NHIS) database, which is a national big data resource in South Korea. Access to NHIS data requires approval from the National Health Insurance Service and is subject to strict data protection regulations. The datasets analyzed during the current study are available from the NHIS upon reasonable request and with appropriate approval, but restrictions apply to the availability of these data, which were used under license for the current study.

Change history

The Results section, the Methods section, and Tables 1 and 3 have been revised.

References

  1. Sohn W, Lee YS, Kim SS, Kim JH, Jin YJ, Kim GA, et al. KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025. Clin Mol Hepatol. 2025;31(Suppl):S1-s31
    Article PubMed PubMed Central Google Scholar
  2. Haam JH, Kim BT, Kim EM, Kwon H, Kang JH, Park JH, et al. Diagnosis of obesity: 2022 update of clinical practice guidelines for obesity by the Korean Society for the study of obesity. J Obes Metab Syndr. 2023;32(2):121–129. https://doi.org/10.7570/jomes23031
    Article PubMed PubMed Central Google Scholar
  3. Kim GA, Moon JH, Kim W. Critical appraisal of metabolic dysfunction-associated steatotic liver disease: implication of janus-faced modernity. Clin Mol Hepatol. 2023;29(4):831–843
    Article PubMed PubMed Central Google Scholar
  4. Finer Z, Lopez C, Sharpton S, Gao Y, Lindsell C, Lister R, et al. Pregnancy does not affect liver chemistries in metabolic dysfunction-associated steatotic liver disease. Hepatol Commun. 2024;8(12):e05087
    Article Google Scholar
  5. Sarkar M, Kushner T. Metabolic dysfunction-associated steatotic liver disease and pregnancy. J Clin Invest. 2025. https://doi.org/10.1172/JCI186426
    Article PubMed PubMed Central Google Scholar
  6. Jung YM, Lee SM, Hong S, Koo JN, Oh IH, Kim BJ, et al. The risk of pregnancy-associated hypertension in women with nonalcoholic fatty liver disease. Liver Int. 2020;40(10):2417–2426. https://doi.org/10.1111/liv.14563
    Article CAS PubMed Google Scholar
  7. Lee SM, Cho GJ, Wi WY, Norwitz ER, Koo BK, Lee J, et al. Metabolic dysfunction-associated fatty liver disease as a risk factor for adverse outcomes in subsequent pregnancy: a nationwide cohort study. Hepatol Int. 2023;17(2):367–376
    Article PubMed Google Scholar
  8. Lee SM, Kim BJ, Koo JN, Norwitz ER, Oh IH, Kim SM, et al. Nonalcoholic fatty liver disease is a risk factor for large-for-gestational-age birthweight. PLoS ONE. 2019;14(8): e0221400. https://doi.org/10.1371/journal.pone.0221400
    Article CAS PubMed PubMed Central Google Scholar
  9. Lee SM, Kwak SH, Koo JN, Oh IH, Kwon JE, Kim BJ, et al. Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus. Diabetologia. 2019;62(2):238–248
    Article CAS PubMed Google Scholar
  10. Lee SM, Jung YM, Choi ES, Kwak SH, Koo JN, Oh IH, et al. Metabolic dysfunction-associated fatty liver disease and subsequent development of adverse pregnancy outcomes. Clin Gastroenterol Hepatol. 2022;20(11):2542–50.e8
    Article PubMed Google Scholar
  11. Jung Y, Lee SM, Lee J, Kim Y, Lee W, Koo JN, et al. Metabolomic profiling reveals early biomarkers of gestational diabetes mellitus and associated hepatic steatosis. Cardiovasc Diabetol. 2025;24(1):125
    Article CAS PubMed PubMed Central Google Scholar
  12. Grieger JA, Bianco-Miotto T, Grzeskowiak LE, Leemaqz SY, Poston L, McCowan LM, et al. Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes: a prospective cohort of nulliparous women. PLoS Med. 2018;15(12): e1002710. https://doi.org/10.1371/journal.pmed.1002710
    Article CAS PubMed PubMed Central Google Scholar
  13. Ajmera VH, Gunderson EP, VanWagner LB, Lewis CE, Carr JJ, Terrault NA. Gestational diabetes mellitus is strongly associated with non-alcoholic fatty liver disease. Am J Gastroenterol. 2016;111(5):658–664. https://doi.org/10.1038/ajg.2016.57
    Article CAS PubMed PubMed Central Google Scholar
  14. Niu C, Zhang J, Khalid N, Zhu K, Syed T, Liu H, et al. Cardiovascular complications during delivery hospitalizations in patients with nonalcoholic fatty liver disease in pregnancy. Eur J Gastroenterol Hepatol. 2024;36(9):1141–1148. https://doi.org/10.1097/MEG.0000000000002802
    Article PubMed Google Scholar
  15. Jung YM, Lee SM, Wi W, Oh MJ, Park JS, Cho GJ, et al. Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: a nationwide study. JHEP Rep. 2024;6(4): 101033. https://doi.org/10.1016/j.jhepr.2024.101033
    Article PubMed PubMed Central Google Scholar
  16. Mishra P, Sadananthan SA, Yaligar J, Tan KH, Chong YS, Gluckman PD, et al. Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age. BMC Med. 2024;22(1):561
    Article CAS PubMed PubMed Central Google Scholar
  17. Lee HH, Lee HA, Kim EJ, Kim HY, Kim HC, Ahn SH, et al. Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease. Gut. 2024;73(3):533–540
    Article CAS PubMed Google Scholar
  18. El Jamaly H, Eslick GD, Weltman M. Systematic review with meta-analysis: non-alcoholic fatty liver disease and the association with pregnancy outcomes. Clin Mol Hepatol. 2022;28(1):52–66
    Article PubMed Google Scholar
  19. Bril F, Kalavalapalli S, Lomonaco R, Frye R, Godinez Leiva E, Cusi K. Insulin resistance is an integral feature of MASLD even in the presence of PNPLA3 variants. JHEP Rep. 2024;6(7): 101092. https://doi.org/10.1016/j.jhepr.2024.101092
    Article PubMed PubMed Central Google Scholar
  20. Guevara-Ramírez P, Paz-Cruz E, Cadena-Ullauri S, Ruiz-Pozo VA, Tamayo-Trujillo R, Felix ML, et al. Molecular pathways and nutrigenomic review of insulin resistance development in gestational diabetes mellitus. Front Nutr. 2023;10:1228703
    Article PubMed PubMed Central Google Scholar
  21. Wang M, Zheng L, Meng Y, Ma S, Zhao D, Xu Y. Broadening horizons: intestinal microbiota as a novel biomarker and potential treatment for hypertensive disorders of pregnancy. Front Cell Infect Microbiol. 2024;14:1446580
    Article CAS PubMed PubMed Central Google Scholar
  22. Kirichenko TV, Markina YV, Sukhorukov VN, Khotina VA, Wu WK, Orekhov AN. A novel insight at atherogenesis: the role of microbiome. Front Cell Dev Biol. 2020;8: 586189. https://doi.org/10.3389/fcell.2020.586189
    Article PubMed PubMed Central Google Scholar
  23. Mishra JS, Zhao H, Zheng J, Kumar S. Sex-specific dysregulation of placental lipid metabolism in preeclampsia. Obstet Gynecol Res. 2024;7(3):49–58
    Article PubMed PubMed Central Google Scholar
  24. Chen S, Wang Y, Wang Z, Tao L, Wang Y, Wei Y, et al. Pre conception dyslipidemia and risk for preeclampsia in women undergoing IVF ET. Sci Rep. 2025;15(1):18454
    Article CAS PubMed PubMed Central Google Scholar
  25. Jowell AR, Sarma AA, Gulati M, Michos ED, Vaught AJ, Natarajan P, et al. Interventions to mitigate risk of cardiovascular disease after adverse pregnancy outcomes: a review. JAMA Cardiol. 2022;7(3):346–355
    Article PubMed PubMed Central Google Scholar
  26. Murray Horwitz ME, Fisher MA, Prifti CA, Rich-Edwards JW, Yarrington CD, White KO, et al. Primary care-based cardiovascular disease risk management after adverse pregnancy outcomes: a narrative review. J Gen Intern Med. 2022;37(4):912–921. https://doi.org/10.1007/s11606-021-07149-x
    Article PubMed PubMed Central Google Scholar
  27. Kim GA, Jeong S, Jang H, Lee DH, Joo SK, Kim W. Metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatotic liver disease with increased alcohol intake increase the risk of developing hepatocellular carcinoma and Incident or decompensated cirrhosis: a Korean nationwide study. Liver Cancer. 2024;13(4):426–437. https://doi.org/10.1159/000535943
    Article CAS PubMed Google Scholar
  28. Moon JH, Jeong S, Jang H, Koo BK, Kim W. Metabolic dysfunction-associated steatotic liver disease increases the risk of incident cardiovascular disease: a nationwide cohort study. EClinicalMedicine. 2023;65: 102292. https://doi.org/10.1016/j.eclinm.2023.102292
    Article PubMed PubMed Central Google Scholar
  29. Han AL. Validation of fatty liver index as a marker for metabolic dysfunction-associated fatty liver disease. Diabetol Metab Syndr. 2022;14(1): 44. https://doi.org/10.1186/s13098-022-00811-2
    Article PubMed PubMed Central Google Scholar
  30. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al. The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6: 33. https://doi.org/10.1186/1471-230X-6-33
    Article CAS PubMed PubMed Central Google Scholar
  31. Cho EJ, Jung GC, Kwak MS, Yang JI, Yim JY, Yu SJ, et al. Fatty liver index for predicting nonalcoholic fatty liver disease in an asymptomatic Korean population. Diagnostics (Basel). 2021. https://doi.org/10.3390/diagnostics11122233
    Article PubMed PubMed Central Google Scholar
  32. Meda C, Dolce A, Della Torre S. Metabolic dysfunction-associated steatotic liver disease across women’s reproductive lifespan and issues. Clin Mol Hepatol. 2025;31(1):327–332
    Article PubMed Google Scholar

Download references

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2025-25458964; 2021R1A2C2005820; RS-2021-NR056442; RS-2022-NR067269; RS-2023-00223831; RS-2024-00440883). And this work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2024-00427361).

Author information

Author notes

  1. Geum Joon Cho and Won Kim have contributed equally as co-corresponding authors.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
    Young Mi Jung, Min-Jeong Oh & Geum Joon Cho
  2. Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
    Young Mi Jung
  3. Department of Statistics, Sungkyunkwan University, Seoul, Korea
    Taesu Kim
  4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
    Dong Hyeon Lee & Won Kim
  5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
    Dong Hyeon Lee & Won Kim

Authors

  1. Young Mi Jung
  2. Taesu Kim
  3. Min-Jeong Oh
  4. Dong Hyeon Lee
  5. Geum Joon Cho
  6. Won Kim

Contributions

Dr. YM Jung, Drs. GJ Cho, and W Kim had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis; Study concept and design: YM Jung, GJ Cho, and W Kim; Acquisition, analysis, or interpretation of data: All authors; Drafting of the manuscript: YM Jung, GJ Cho, and W Kim; Critical revision of the manuscript for important intellectual content: All authors; Statistical analysis: YM Jung, GJ Cho, and T Kim; Study supervision: GJ Cho and W Kim; Guarantor: W Kim.

Corresponding authors

Correspondence toGeum Joon Cho or Won Kim.

Ethics declarations

Conflict of interest

None to declare.

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Korea University Guro Hospital (IRB approval number: 2025GR0092). Due to the retrospective nature of this study and the use of de-identified patient data, the requirement for informed consent was waived by the ethics committee. This study used de-identified retrospective data, and no individual patient data that could lead to identification is presented.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised to correct the Results section, the Methods section, and Tables 1 and 3.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Cite this article

Jung, Y.M., Kim, T., Oh, MJ. et al. Metabolic dysfunction-associated steatotic liver disease and adverse pregnancy outcomes: a nationwide cohort study.Hepatol Int (2025). https://doi.org/10.1007/s12072-025-10972-7

Download citation

Keywords