Effects of Gestational Diabetes Mellitus on Fetal Liver Length: A Systematic Review and Meta-Analysis
-
Sahar Ardalan Khales
,
Abdolhalim Rajabi
,
Masoud Golalipour
,
Gholamreza Roshandel
,
Mohammad Jafar Golalipour
Abstract
Background: Gestational diabetes mellitus (GDM) is a serious pregnancy complication that can affect various organs and organ systems of the mother and fetus. In diabetic mothers, increased blood glucose delivery to the fetus leads to fetal hyperglycemia and hyperinsulinemia, which promotes the growth of insulin-dependent organs such as the liver. Therefore, this systematic review and meta-analysis was conducted to more precisely estimate the association between GDM and fetal liver length (FLL).
Methods: Six electronic databases (PubMed, Scopus, Web of Science, ProQuest, Cochrane, and Wiley) were searched up to Aug 2023. Two reviewers independently extracted data and assessed the risk of bias using the Newcastle–Ottawa Scale. The pooled weighted and standardized mean differences in FLL were calculated using random-effects models. Heterogeneity, subgroup analysis, and publication bias were also assessed using funnel plots. All statistical analyses were performed using Stata Version 16.0.
Results: Twelve articles were included in the final meta-analysis. GDM was associated with increased FLL, as assessed by ultrasound, in both the second (SMD=1.56; 95% CI: 1.04, 2.08; P<0.001) and third (SMD=0.84; 95% CI: 0.07, 1.61; P<0.001) trimesters of pregnancy. The pooled mean difference in FLL between the GDM and non-GDM groups was 4.85 mm (WMD=4.85; 95% CI: 3.26, 6.45), indicating larger liver size in fetuses from mothers with GDM.
Conclusion: GDM is a significant risk factor for increased FLL, as assessed by ultrasound, which may reflect fetal overgrowth and metabolic dysfunction.
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13. Hod M, Kapur A, Sacks DA, et al (2015). The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet, 131 Suppl 3:S173-211.
14. Group HSCR (2009). Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics. Diabetes, 58 (2):453-9.
15. Blotsky AL, Rahme E, Dahhou M, et al (2019). Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study. CMAJ, 191 (15):E410-E417.
16. Wang BB, Xue M (2023). Early neonatal complications in pregnant women with gestational diabetes mellitus and the effects of glycemic control on neonatal infection. World J Diabetes, 14 (9):1393-1402.
17. Perovic M, Gojnic M, Arsic B, et al (2015). Relationship between mid-trimester ultrasound fetal liver length measurements and gestational diabetes mellitus. J Diabetes, 7 (4):497-505.
18. Pedersen J (1954). Weight and length at birth of infants of diabetic mothers. Acta Endocrinol (Copenh), 16(4):330-42.
19. Langer O (2000). Fetal macrosomia: etiologic factors. Clin Obstet Gynecol, 43 (2):283-297.
20. Larciprete G, Valensise H, Vasapollo B, et al (2003). Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies. Ultrasound Obstet Gynecol, 22 (6):591-597.
21. Khoury JC, Dolan LM, VanDyke R, et al (2012). Fetal development in women with diabetes: imprinting for a life-time? J Matern Fetal Neonatal Med, 25 (1):11-14.
22. Gojnic M, Stefanovic T, Perovic M, et al (2012). Prediction of fetal macrosomia with ultrasound parameters and maternal glycemic controls in gestational diabetes mellitus. Clin Exp Obstet Gynecol, 39 (4):512-515.
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26. Rahman N, Sultana J, Abedin N, et al (2016). Ultrasonographic Evaluation of Foetal Hepatic Length in Non-diabetic and Gestational Diabetic Mother in 2nd Trimester. BJRI, 24:1.
27. Showman H, Al-Rawi H, Zghair M (2019). The value of mid-trimester fetal liver length measurement in prediction of gestational diabetes in Iraqi women. South African Journal of Obstetrics and Gynaecology, 25 (3):100-102.
28. Mačkić M, Gojnić M, Stefanović T, et al (2013). Correlation of maternal BMI with fetal liver ultrasound measurements in gestational diabetes mellitus. Materia Medica, 29 (2):837-840.
29. Fattah EAAEI (2017). Diagnostic ability of the fetal ultrasonographic parameters in screening for gestational diabetes. MOJ Womens Health, 6(1):344‒356.
30. Cevik M, Deveer R (2020). The role of ductus venosus doppler, fetal liver length and placental thickness in gestational diabetes. Med Science, 91:136-9.
31. Abd Elwahab AM, Alkafrawy ME, Abd Elghany AM (2018). The Role of Mid-Trimester Ultrasound Fetal Liver Length Measurement in Prediction of Gestational Diabetes Mellitus. Nat Sci, 16(5):90-94.
32. Gharib WF, Huissen WM (2019). Fetal Liver Length and State of Maternal Glycemic Control. Austin J Obstet Gynecol, 6(4): 1144.
33. Hanim H, Elhassany A, Mohammad A, Abd Ei (2021). Value of Fetal Ultrasonographic Study in Screening for Gestational Diabetes Mellitus. https://www.researchgate.net/publication/353305656_Value_of_Fetal_Ultrasonographic_Study_in_Screening_for_Gestational_Diabetes_Mellitus
34. Stanirowski PJ, Majewska A, Lipa M, et al (2021). Ultrasound evaluation of the fetal fat tissue, heart, liver and umbilical cord measurements in pregnancies complicated by gestational and type 1 diabetes mellitus: potential application in the fetal birth-weight estimation and prediction of the fetal macrosomia. Diabetol Metab Syndr, 13:22.
35. Pouya EK, Keshavarz E, Moradpour M, et al (2022). The Relationship of Fetal Adrenal Gland Size with Fetal Liver Length and Fetal Abdominal Wall Fat Thickness in Mothers with and Without Gestational Diabetes. J Trauma Care, 7(1): 1037.
36. Venkatesh KK ,London MB (2021). Diagnosis and Management of Gestational Diabetes. Contemp OB/GYN J, 66 (5):1-10.
37. Reitzle L, Schmidt C, Heidemann C, et al (2021). Gestational diabetes in Germany: Development of screening participation and prevalence. J Health Monit, 6 (2):3-18.
38. Anderson N, Notley E, Graham P, et al (2008). Reproducibility of sonographic assessment of fetal liver length in dia-betic pregnancies. Ultrasound Obstet Gynecol, 31 (5):529-534.
2. International Diabetes Federation Diabetes Atlas (2021). Available from: https://diabetesatlas.org
3. Saeedi P, Petersohn I, Salpea P, et al (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract,157:107843.
4. World Health Organization (1999). Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus. World Health Organization. https://iris.who.int/handle/10665/66040
5. American Diabetes Association (2020). 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2020. Diabetes Care, 43(Suppl 1):S14-S31.
6. Wang H, Li N, Chivese T, et al (2022). IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group’s Criteria. Diabetes Res Clin Pract, 183:109050.
7. Karasneh RA, Migdady FH, Alzoubi KH, et al (2021). Trends in maternal characteristics, and maternal and neonatal outcomes of women with gestational diabetes: A study from Jordan. Ann Med Surg (Lond), 67:102469.
8. Group HSCR, Metzger BE, Lowe LP, et al (2008). Hyperglycemia and adverse pregnancy outcomes. N Engl J Med, 358 (19):1991-2002.
9. Muche AA, Olayemi OO, Gete YK (2020). Effects of gestational diabetes mellitus on risk of adverse maternal outcomes: a prospective cohort study in Northwest Ethiopia. BMC Pregnancy Childbirth, 20 (1):73.
10. McIntyre HD, Catalano P, Zhang C, et al (2019). Gestational diabetes mellitus. Nat Rev Dis Primers, 5(1):47.
11. McKenzie-Sampson S, Paradis G, Healy-Profitos J, et al (2018). Gestational diabetes and risk of cardiovascular disease up to 25 years after pregnancy: a retrospective cohort study. Acta Diabetol, 55 (4):315-322.
12. Kramer CK, Campbell S, Retnakaran R (2019). Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis. Diabetologia, 62 (6):905-914.
13. Hod M, Kapur A, Sacks DA, et al (2015). The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet, 131 Suppl 3:S173-211.
14. Group HSCR (2009). Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics. Diabetes, 58 (2):453-9.
15. Blotsky AL, Rahme E, Dahhou M, et al (2019). Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study. CMAJ, 191 (15):E410-E417.
16. Wang BB, Xue M (2023). Early neonatal complications in pregnant women with gestational diabetes mellitus and the effects of glycemic control on neonatal infection. World J Diabetes, 14 (9):1393-1402.
17. Perovic M, Gojnic M, Arsic B, et al (2015). Relationship between mid-trimester ultrasound fetal liver length measurements and gestational diabetes mellitus. J Diabetes, 7 (4):497-505.
18. Pedersen J (1954). Weight and length at birth of infants of diabetic mothers. Acta Endocrinol (Copenh), 16(4):330-42.
19. Langer O (2000). Fetal macrosomia: etiologic factors. Clin Obstet Gynecol, 43 (2):283-297.
20. Larciprete G, Valensise H, Vasapollo B, et al (2003). Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies. Ultrasound Obstet Gynecol, 22 (6):591-597.
21. Khoury JC, Dolan LM, VanDyke R, et al (2012). Fetal development in women with diabetes: imprinting for a life-time? J Matern Fetal Neonatal Med, 25 (1):11-14.
22. Gojnic M, Stefanovic T, Perovic M, et al (2012). Prediction of fetal macrosomia with ultrasound parameters and maternal glycemic controls in gestational diabetes mellitus. Clin Exp Obstet Gynecol, 39 (4):512-515.
23. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 372:n71.
24. Peterson J, Welch V, Losos M, et al (2011). The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute, 2 (1):1-12.
25. Mirghani H, Zayed R, Thomas L, et al (2007). Gestational diabetes mellitus: fetal liver length measurements between 21and 24 weeks' gestation. J Clin Ultrasound, 35 (1):34-37.
26. Rahman N, Sultana J, Abedin N, et al (2016). Ultrasonographic Evaluation of Foetal Hepatic Length in Non-diabetic and Gestational Diabetic Mother in 2nd Trimester. BJRI, 24:1.
27. Showman H, Al-Rawi H, Zghair M (2019). The value of mid-trimester fetal liver length measurement in prediction of gestational diabetes in Iraqi women. South African Journal of Obstetrics and Gynaecology, 25 (3):100-102.
28. Mačkić M, Gojnić M, Stefanović T, et al (2013). Correlation of maternal BMI with fetal liver ultrasound measurements in gestational diabetes mellitus. Materia Medica, 29 (2):837-840.
29. Fattah EAAEI (2017). Diagnostic ability of the fetal ultrasonographic parameters in screening for gestational diabetes. MOJ Womens Health, 6(1):344‒356.
30. Cevik M, Deveer R (2020). The role of ductus venosus doppler, fetal liver length and placental thickness in gestational diabetes. Med Science, 91:136-9.
31. Abd Elwahab AM, Alkafrawy ME, Abd Elghany AM (2018). The Role of Mid-Trimester Ultrasound Fetal Liver Length Measurement in Prediction of Gestational Diabetes Mellitus. Nat Sci, 16(5):90-94.
32. Gharib WF, Huissen WM (2019). Fetal Liver Length and State of Maternal Glycemic Control. Austin J Obstet Gynecol, 6(4): 1144.
33. Hanim H, Elhassany A, Mohammad A, Abd Ei (2021). Value of Fetal Ultrasonographic Study in Screening for Gestational Diabetes Mellitus. https://www.researchgate.net/publication/353305656_Value_of_Fetal_Ultrasonographic_Study_in_Screening_for_Gestational_Diabetes_Mellitus
34. Stanirowski PJ, Majewska A, Lipa M, et al (2021). Ultrasound evaluation of the fetal fat tissue, heart, liver and umbilical cord measurements in pregnancies complicated by gestational and type 1 diabetes mellitus: potential application in the fetal birth-weight estimation and prediction of the fetal macrosomia. Diabetol Metab Syndr, 13:22.
35. Pouya EK, Keshavarz E, Moradpour M, et al (2022). The Relationship of Fetal Adrenal Gland Size with Fetal Liver Length and Fetal Abdominal Wall Fat Thickness in Mothers with and Without Gestational Diabetes. J Trauma Care, 7(1): 1037.
36. Venkatesh KK ,London MB (2021). Diagnosis and Management of Gestational Diabetes. Contemp OB/GYN J, 66 (5):1-10.
37. Reitzle L, Schmidt C, Heidemann C, et al (2021). Gestational diabetes in Germany: Development of screening participation and prevalence. J Health Monit, 6 (2):3-18.
38. Anderson N, Notley E, Graham P, et al (2008). Reproducibility of sonographic assessment of fetal liver length in dia-betic pregnancies. Ultrasound Obstet Gynecol, 31 (5):529-534.
| Files | ||
| Issue | Vol 54 No 2 (2025) | |
| Section | Review Article(s) | |
| Keywords | ||
| Fetus Gestational diabetes mellitus Liver Meta-analysis | ||
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How to Cite
1.
Ardalan Khales S, Rajabi A, Golalipour M, Roshandel G, Golalipour MJ. Effects of Gestational Diabetes Mellitus on Fetal Liver Length: A Systematic Review and Meta-Analysis. Iran J Public Health. 2025;54(2):321-332.
