Nonalcoholic fatty liver disease-based risk prediction of adverse pregnancy outcomes: Ready for prime time?

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Clin Mol Hepatol. 2022;28(1):47-49
Publication date (electronic) : 2021 November 30
doi :
1Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
3Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
Corresponding author : Won Kim Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea Tel: +82-2-870-2233, Fax: +82-2-831-2826 E-mail:
Editor: Byoung Kuk Jang, Keimyung University School of Medicine, Korea
Received 2021 October 27; Revised 2021 November 25; Accepted 2021 November 30.

There is a growing body of evidence that nonalcoholic fatty liver disease (NAFLD) is associated with further development of cardiometabolic disease [1]. Pregnancy is deemed a window period to predict further metabolic or cardiovascular disease later in life. Physiological changes during pregnancy, such as circulatory volume increases, inflammatory changes, insulin resistance, and dyslipidemia, can present challenges to pregnant women [2]. Because of these changes, pregnancy complications can develop, and it has been reported that women who experience pregnancy complications are likely to develop further metabolic or cardiovascular disease after pregnancy [3-8]. Indeed, pregnancy is also a period of opportunity to identify women at high risk for long-term metabolic or cardiovascular disease [9].

Recently, there have been several reports on pregnancy outcomes in women with NAFLD. NAFLD has been reported to be associated with diverse pregnancy complications, such as gestational diabetes mellitus (GDM), fetal overgrowth, or hypertensive disease during pregnancy [10-13]. In this issue of Clinical and Molecular Hepatology, El Jamaly et al. [14] conducted a systematic review of the literature to determine the current evidence regarding maternal and fetal outcomes in pregnant women with NAFLD. In the review of 22 studies that included 13,641 female patients with NAFLD, women with NAFLD were at increased risk of baseline diabetes mellitus (odds ratio [OR], 6.00; 95% confidence interval [CI], 2.21–16.31), baseline hypertension (OR, 3.75; 95 CI, 2.13–6.59), gestational hypertension (OR, 1.83; 95% CI, 1.03–3.26), and preeclampsia (OR, 2.43; 95% CI, 2.21–16.31). Moreover, NALFD was associated with the risk of gestational diabetes (OR, 3.78; 95% CI, 2.21–6.44 for post history of gestational diabetes; OR, 2.81; 95% CI, 1.58–5.02 for current gestational diabetes), premature birth (OR, 2.02; 95% CI, 1.44–2.85), large for gestational age birth (OR, 2.01; 95% CI, 1.72–2.37), and history of prior miscarriage or abortion (OR, 1.15; 95% CI, 1.02–1.30). Overall, the authors showed that NAFDL was associated with increased risk of maternal diabetic or hypertensive complications and other adverse fetal outcomes, providing informative evidence in clinical management of women with NAFLD.

The current study is the first meta-analysis that reports a correlation between NAFLD and pregnancy outcomes. However, the authors could not exclude other liver-related competing conditions (hepatitis or liver transplantation), and some of the studies analyzed did not disclose the method of NAFLD diagnosis. Nevertheless, the large sample size and the quality of the included studies support that the estimated effect from the current meta-analysis is close to the true effect.

Based on the current and previous reports, a consensus can be drawn that NAFLD is a definite risk factor for several adverse pregnancy outcomes. While the traditional risk stratification system recommended by the practice guidelines can identify only a handful of pregnant women who eventually develop GDM or preeclampsia [13,15], the incorporation of NAFLD into the preexisting risk stratification model improves the predictive performance for adverse pregnancy outcomes [16]. However, whether the early identification of NAFLD in pregnant women should be routinely implemented remains controversial. The cost-effectiveness analysis should be performed first, as the confirmative diagnosis of NAFLD requires either radiological or histological examination, which may be difficult to conduct in prenatal care.

The effect of NAFLD during pregnancy on the fetus is another important issue that needs to be addressed in future studies. As shown by the increased risk of GDM or fetal overgrowth in pregnant women with NAFLD, it is biologically plausible that the metabolic changes in women with NAFLD may also affect the fetus in utero. Consequently, fetal growth disturbance may be correlated with long-term cardiometabolic risk, such as obesity, diabetes mellitus, and cardiovascular disease, later in life [17]. Therefore, further studies are warranted to investigate the metabolic disturbance of the fetus in women with NAFLD and its impact in the neonatal, infant, and adult periods.


Authors’ contributions

All authors were responsible for the interpretation of data, drafting and critical revision of the manuscript.

Conflicts of Interest: The authors have no conflicts to disclose.


This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2021R1A2C2005820 and 2021M3A9E4021818).



confidence interval


gestational diabetes mellitus


nonalcoholic fatty liver disease


odds ratio


1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73–84.
2. Sattar N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ 2002;325:157–160.
3. Kramer CK, Campbell S, Retnakaran R. Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis. Diabetologia 2019;62:905–914.
4. Kessous R, Shoham-Vardi I, Pariente G, Sherf M, Sheiner E. An association between gestational diabetes mellitus and long-term maternal cardiovascular morbidity. Heart 2013;99:1118–1121.
5. Fadl H, Magnuson A, Östlund I, Montgomery S, Hanson U, Schwarcz E. Gestational diabetes mellitus and later cardiovascular disease: a Swedish population based case-control study. BJOG 2014;121:1530–1536.
6. Savitz DA, Danilack VA, Elston B, Lipkind HS. Pregnancy-induced hypertension and diabetes and the risk of cardiovascular disease, stroke, and diabetes hospitalization in the year following delivery. Am J Epidemiol 2014;180:41–44.
7. Wu P, Mamas MA, Gulati M. Pregnancy as a predictor of maternal cardiovascular disease: the era of CardioObstetrics. J Womens Health (Larchmt) 2019;28:1037–1050.
8. Søndergaard MM, Hlatky MA, Stefanick ML, Vittinghoff E, Nah G, Allison M, et al. Association of adverse pregnancy outcomes with risk of atherosclerotic cardiovascular disease in postmenopausal women. JAMA Cardiol 2020;5:1390–1398.
9. Tooher J, Thornton C, Makris A, Ogle R, Korda A, Hennessy A. All hypertensive disorders of pregnancy increase the risk of future cardiovascular disease. Hypertension 2017;70:798–803.
10. 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;62:238–248.
11. 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:e0221400.
12. 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;40:2417–2426.
13. Hong S, Lee SM, Kwak SH, Kim BJ, Koo JN, Oh IH, et al. A comparison of predictive performances between old versus new criteria in a risk-based screening strategy for gestational diabetes mellitus. Diabetes Metab J 2020;44:726–736.
14. 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;28:52–66.
15. Chaemsaithong P, Sahota DS, Poon LC. First trimester preeclampsia screening and prediction. Am J Obstet Gynecol 2020;Jul. 16. doi: 10.1016/j.ajog.2020.07.020.
16. Lee SM, Hwangbo S, Norwitz ER, Koo JN, Oh IH, Choi ES, et al. Nonalcoholic fatty liver disease and early prediction of gestational diabetes using machine learning methods. Clin Mol Hepatol 2022;28:105–116.
17. Barker DJ. Adult consequences of fetal growth restriction. Clin Obstet Gynecol 2006;49:270–283.

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