Non-alcoholic fatty liver disease in pregnancy, paving the way for adverse pregnancy outcome risk assessment

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Clin Mol Hepatol. 2022;28(1):50-51
Publication date (electronic) : 2021 November 22
doi :
Department of Obstetrics and Gynecology, Institute of Women’s Medical Life Science, Yonsei University College of Medicine, Seoul, Korea
Corresponding author : Ja Young Kwon Department of Obstetrics and Gynecology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2228-2245, Fax: +82-2-313-8350 E-mail:
Editor: Seung Up Kim, Yonsei University College of Medicine, Korea
Received 2021 November 16; Accepted 2021 November 17.

According to the current obstetrical practice, blood chemistry tests, such as liver function tests or cholesterol panel, are not included in the initial blood test at first prenatal visit [1]. Moreover, elevated serum cholesterol or triglyceride levels in pregnant women are not taken seriously but rather considered as normal alteration in lipid physiology caused by pregnancy hormones [2]. Therefore, in practice, screening for non-alcoholic fatty liver disease (NAFLD) in pregnancy is easily overlooked and disease-related pregnancy complication are often underestimated.

In the January 2022 issue of the Clinical and Molecular Hepatology, El Jamaly et al. [3] reported a systemic review and meta-analysis to assess the association between NAFLD and adverse maternal and fetal outcomes, which provided compelling evidence to support that NAFLD is independently associated with gestational diabetes (GDM) as well as pregnancy-induced hypertension (PIH), including gestational hypertension, preeclampsia (PE), and eclampsia (odds ratio, 2.81, 1.83, 3.24, and 3.91, respectively) [3]. Certainly, such finding increases the awareness about NAFLD and adverse pregnancy outcome, but at the same time, raises questions in the context of obstetric care. Should we consider NAFLD in the risk stratification for GDM or PE? Who should be subjected to screening for NAFLD during pregnancy or at postpartum? How should women with NAFLD, having such high metabolic risk, be managed differently during pregnancy? Is there a preventive strategy available for pregnancy-induced diabetes mellitus or hypertension? More studies should follow to assess the potential benefit, or the lack of benefit, of screening a population for NAFLD when the diagnosis is made.

Care should be taken in the interpretation of data herein. The participants were enrolled in this meta-analysis between 1992 and 2019, which is quite a wide time frame [3]. During this period, new GDM screening strategy and diagnostic criteria were introduced. With the adoption of the International Association of the Diabetes and Pregnancy Study Groups diagnostic criteria for the 75-g oral glucose tolerance test (OGTT) in late 2000s, the diagnostic yield for GDM increased by 12% [4]. Meanwhile, the American College of Obstetricians and Gynecologists continued to recommend Carpenter-Coustan or National Diabetes Data Group diagnostic threshold for the 100-g OGTT [5,6]. Also, the diagnostic criteria for PE were revised in 2013 to encompass other features of end-organ dysfunction [7,8]. As different criteria will identify different degree of patients, the prevalence of adverse outcomes may differ significantly according to the study period [9]. Therefore, the study period and diagnostic criteria may need to be considered in the risk adjustment.

Patients with conditions that predispose to insulin resistance (e.g., polycystic ovarian syndrome [PCOS]) [10] are considered at high risk for GDM and subjected to earlier GDM screening at the initial prenatal visit [11]. We cannot argue with the fact that NAFLD is a manifestation of metabolic syndrome and presence of insulin resistance [12-14]. Therefore, as with PCOS, a patient with NAFLD may also be a potential candidate for stringent GDM screening with the intent of optimizing gestational outcome. However, the current lack of consistency regarding the diagnosis of NAFLD in pregnancy remains a major concern. While ultrasound is commonly employed, due to its low sensitivity and operator-dependency, there is no consensus on the ultrasound criteria to diagnose fatty liver [15-17]. Therefore, building a consensus on the diagnostic criteria, or possibly developing a new ultrasonographic grading system based on the specific relationships to the risk of adverse pregnancy outcome, is warranted.


Conflicts of Interest: The author has no conflicts to disclose.



gestational diabetes


non-alcoholic fatty liver disease


oral glucose tolerance test


polycystic ovarian syndrome




pregnancy-induced hypertension


1. Cunningham F, Leveno KJ, Bloom SL, Dashe JS, Hoffman BL, Casey BM, et al. Williams Obstetrics, 25e New York: McGraw Hill; 2018. p. 160–179.
2. Lain KY, Catalano PM. Metabolic changes in pregnancy. Clin Obstet Gynecol 2007;50:938–948.
3. 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.
4. Shang M, Lin L. IADPSG criteria for diagnosing gestational diabetes mellitus and predicting adverse pregnancy outcomes. J Perinatol 2014;34:100–104.
5. ACOG practice bulletin No. 190: gestational diabetes mellitus. Obstet Gynecol 2018;131:e49–e64.
6. Harper LM, Mele L, Landon MB, Carpenter MW, Ramin SM, Reddy UM, et al. Carpenter-Coustan compared with National Diabetes Data Group criteria for diagnosing gestational diabetes. Obstet Gynecol 2016;127:893–898.
7. Tranquilli AL, Dekker G, Magee L, Roberts J, Sibai BM, Steyn W, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens 2014;4:97–104.
8. ACOG practice bulletin No. 202: gestational hypertension and preeclampsia. Obstet Gynecol 2019;133:1.
9. Reddy M, Fenn S, Rolnik DL, Mol BW, da Silva Costa F, Wallace EM, et al. The impact of the definition of preeclampsia on disease diagnosis and outcomes: a retrospective cohort study. Am J Obstet Gynecol 2021;224:217.e1–217.e11.
10. Giannakou K, Evangelou E, Yiallouros P, Christophi CA, Middleton N, Papatheodorou E, et al. Risk factors for gestational diabetes: an umbrella review of meta-analyses of observational studies. PLoS One 2019;14:e0215372.
11. Palomba S, de Wilde MA, Falbo A, Koster MP, La Sala GB, Fauser BC. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update 2015;21:575–592.
12. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30:1212–1218.
13. Machado MV, Ferreira DM, Castro RE, Silvestre AR, Evangelista T, Coutinho J, et al. Liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance. PLoS One 2012;7:e31738.
14. Yki-Järvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2014;2:901–910.
15. Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: a systematic review with comparative analysis. World J Gastroenterol 2018;24:3361–3373.
16. Mishra P, Younossi ZM. Abdominal ultrasound for diagnosis of nonalcoholic fatty liver disease (NAFLD). Am J Gastroenterol 2007;102:2716–2717.
17. Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002;123:745–750.

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