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Can First Trimester Plasma Protein A Level Predict Gestational Diabetes Mellitus

Year 2025, , 240 - 244, 15.01.2025
https://doi.org/10.37990/medr.1598384

Abstract

Aim: Gestational diabetes mellitus (GDM), a condition with multifactorial etiology and adverse perinatal consequences, affects approximately 15% of pregnancies globally, with higher prevalence in certain populations, such as Türkiye. The role of pregnancy-associated plasma protein-A (PAPP-A) on GDM risk remains unclear. This prospective study aimed to assess whether first-trimester maternal PAPP-A levels are predictive of GDM.
Material and Method: This study involved 573 singleton pregnancies in women aged 18 to 45 years, conducted at a tertiary maternity hospital. PAPP-A and free β-hCG were assessed, and GDM screening was carried out using a 75 g oral glucose tolerance test. Comprehensive statistical analyses were applied to evaluate the findings.
Results: Of the participants, 28.09% were diagnosed with GDM. GDM group exhibited significantly lower PAPP-A MoM levels compared to controls (p=0.042). ROC analysis revealed limited predictive utility, with a PAPP-A threshold of 0.99 demonstrating 52.3% sensitivity and 51.7% specificity. Logistic regression identified low PAPP-A levels, advanced maternal age, and higher body mass index (BMI) as independent GDM risk factors.
Conclusion: While the findings underscore a potential association between PAPP-A levels and GDM, the predictive capacity of PAPP-A alone is modest. Future research should explore integrated predictive models incorporating PAPP-A and other biomarkers for improved early GDM screening.

Ethical Statement

The research protocol received approval from the Local Ethics Committee (approval number E2-21-513).

Supporting Institution

No

Thanks

No

References

  • Yanachkova V, Staynova R, Stankova T, Kamenov Z. Placental growth factor and pregnancy-associated plasma protein-A as potential early predictors of gestational diabetes mellitus. Medicina (Kaunas). 2023;59:398.
  • American Diabetes Association Professional Practice Committee. 2. classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45:S17-38.
  • Modzelewski R, Stefanowicz-Rutkowska MM, Matuszewski W, Bandurska-Stankiewicz EM. Gestational diabetes mellitus-recent literature review. J Clin Med. 2022;11:5736.
  • Aktün HL, Uyan D, Yorgunlar B, et al. Gestational diabetes mellitus screening and outcomes. J Turk Ger Gynecol Assoc. 2015;16:25-9.
  • Balık G, Şahin Baydur S, Tekin Bayoğlu Y, et al. The prevalence of gestational diabetes mellitus in pregnants who applied to the maternity outpatient clinic of a university hospital. EJM. 2016;55:55-8.
  • Karaçam Z, Çelİk D. The prevalence and risk factors of gestational diabetes mellitus in Turkey: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2021;34:1331-41.
  • Sezer H, Yazici D, Canbaz HB, et al. The frequency of acceptance of oral glucose tolerance test in Turkish pregnant women: a single tertiary center results. North Clin Istanb. 2022;9:140-8.
  • Patil M, Panchanadikar TM, Wagh G. Variation of papp-a level in the first trimester of pregnancy and its clinical outcome. J Obstet Gynaecol India. 2014;64:116-9.
  • Wu YT, Zhang CJ, Mol BW, et al. Early prediction of gestational diabetes mellitus in the Chinese population via advanced machine learning. J Clin Endocrinol Metab. 2021;106:e1191-205.
  • Saruhan Z, Ozekinci M, Simsek M, et al. Association of first trimester low PAPP-A levels with adverse pregnancy outcomes. Clin Exp Obstet Gynecol. 2012;39:225-8.
  • Petry CJ, Hughes IA, Ong KK. Increased basal insulin sensitivity in late pregnancy in women carrying a male fetus: a cohort study. Biol Sex Differ. 2022;13:20.
  • Rojas-Rodriguez R, Ziegler R, DeSouza T, et al. PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans. Sci Transl Med. 2020;12:eaay4145.
  • Savvidou MD, Syngelaki A, Muhaisen M, et al. First trimester maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus. Bjog. 2012;119:410-6.
  • Cheuk QK, Lo TK, Wong SF, et al. Association between pregnancy-associated plasma protein- A levels in the first trimester and gestational diabetes mellitus in Chinese women. Hong Kong Med J. 2016;22:30-8.
  • Visconti F, Quaresima P, Chiefari E, et al. First trimester combined test (FTCT) as a predictor of gestational diabetes mellitus. Int J Environ Res Public Health. 2019;16:3654.
  • Sweeting AN, Wong J, Appelblom H, et al. A novel early pregnancy risk prediction model for gestational diabetes mellitus. Fetal Diagn Ther. 2019;45:76-84.
  • Borna S, Ashrafzadeh M, Ghaemi M, et al. Correlation between PAPP-A serum levels in the first trimester of pregnancy with the occurrence of gestational diabetes, a multicenter cohort study. BMC Pregnancy Childbirth. 2023;23:847.
  • Gastaldelli A, Gaggini M, DeFronzo RA. Role of adipose tissue insulin resistance in the natural history of type 2 diabetes: results from the San Antonio metabolism study. Diabetes. 2017;66:815-22.
  • Caliskan R, Atis A, Aydin Y, et al. PAPP-A concentrations change in patients with gestational diabetes. Journal of Obstetrics and Gynaecology. 2020;40:190-4.
  • Takele WW, Vesco KK, Josefson J, et al. Effective interventions in preventing gestational diabetes mellitus: a systematic review and meta-analysis. Commun Med (Lond). 2024;4:75.
  • Xiao D, Chenhong W, Yanbin X, et al. Gestational diabetes mellitus and first trimester pregnancy-associated plasma protein A: a case-control study in a Chinese population. J Diabetes Investig. 2018;9:204-10.
  • Ramezani S, Doulabi MA, Saqhafi H, et al. Prediction of gestational diabetes by measuring the levels of pregnancy associated plasma protein-A (PAPP-A) during gestation weeks 11-14. J Reprod Infertil. 2020;21:130-7.
  • Ren Z, Zhe D, Li Z, et al. Study on the correlation and predictive value of serum pregnancy- associated plasma protein A, triglyceride and serum 25-hydroxyvitamin D levels with gestational diabetes mellitus. World J Clin Cases. 2020;8:864-73.
  • Talasaz ZH, Sadeghi R, Askari F, et al. First trimesters pregnancy-associated plasma protein-A levels value to predict gestational diabetes mellitus: a systematic review and meta-analysis of the literature. Taiwan J Obstet Gynecol. 2018;57:181-9.
  • Yanachkova VE, Staynova R, Bochev I, et al. Potential role of biochemical placentation markers - pregnancy associated plasma protein-A and human chorionic gonadotropin for early gestational diabetes screening - a pilot study. Ginekol Pol. 2021 Sep 20. doi: 10.5603/GP.a2021.0129. [Epub ahead of print].
  • Husslein H, Lausegger F, Leipold H, et al. Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11-14 weeks of gestation. J Matern Fetal Neonatal Med. 2012;25:2230-3.
  • Kantomaa T, Vääräsmäki M, Gissler M, et al. First trimester maternal serum PAPP-A and free β-hCG levels and risk of SGA or LGA in women with and without GDM. BMC Pregnancy Childbirth. 2024;24:580.
  • Leung TY, Spencer K, Leung TN, et al. Higher median levels of free β-hCG and PAPP-A in the first trimester of pregnancy in a chinese ethnic group: implication for first trimester combined screening for down’s syndrome in the Chinese population. Fetal Diagn Ther. 2005;21:140-3.
Year 2025, , 240 - 244, 15.01.2025
https://doi.org/10.37990/medr.1598384

Abstract

References

  • Yanachkova V, Staynova R, Stankova T, Kamenov Z. Placental growth factor and pregnancy-associated plasma protein-A as potential early predictors of gestational diabetes mellitus. Medicina (Kaunas). 2023;59:398.
  • American Diabetes Association Professional Practice Committee. 2. classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45:S17-38.
  • Modzelewski R, Stefanowicz-Rutkowska MM, Matuszewski W, Bandurska-Stankiewicz EM. Gestational diabetes mellitus-recent literature review. J Clin Med. 2022;11:5736.
  • Aktün HL, Uyan D, Yorgunlar B, et al. Gestational diabetes mellitus screening and outcomes. J Turk Ger Gynecol Assoc. 2015;16:25-9.
  • Balık G, Şahin Baydur S, Tekin Bayoğlu Y, et al. The prevalence of gestational diabetes mellitus in pregnants who applied to the maternity outpatient clinic of a university hospital. EJM. 2016;55:55-8.
  • Karaçam Z, Çelİk D. The prevalence and risk factors of gestational diabetes mellitus in Turkey: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2021;34:1331-41.
  • Sezer H, Yazici D, Canbaz HB, et al. The frequency of acceptance of oral glucose tolerance test in Turkish pregnant women: a single tertiary center results. North Clin Istanb. 2022;9:140-8.
  • Patil M, Panchanadikar TM, Wagh G. Variation of papp-a level in the first trimester of pregnancy and its clinical outcome. J Obstet Gynaecol India. 2014;64:116-9.
  • Wu YT, Zhang CJ, Mol BW, et al. Early prediction of gestational diabetes mellitus in the Chinese population via advanced machine learning. J Clin Endocrinol Metab. 2021;106:e1191-205.
  • Saruhan Z, Ozekinci M, Simsek M, et al. Association of first trimester low PAPP-A levels with adverse pregnancy outcomes. Clin Exp Obstet Gynecol. 2012;39:225-8.
  • Petry CJ, Hughes IA, Ong KK. Increased basal insulin sensitivity in late pregnancy in women carrying a male fetus: a cohort study. Biol Sex Differ. 2022;13:20.
  • Rojas-Rodriguez R, Ziegler R, DeSouza T, et al. PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans. Sci Transl Med. 2020;12:eaay4145.
  • Savvidou MD, Syngelaki A, Muhaisen M, et al. First trimester maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus. Bjog. 2012;119:410-6.
  • Cheuk QK, Lo TK, Wong SF, et al. Association between pregnancy-associated plasma protein- A levels in the first trimester and gestational diabetes mellitus in Chinese women. Hong Kong Med J. 2016;22:30-8.
  • Visconti F, Quaresima P, Chiefari E, et al. First trimester combined test (FTCT) as a predictor of gestational diabetes mellitus. Int J Environ Res Public Health. 2019;16:3654.
  • Sweeting AN, Wong J, Appelblom H, et al. A novel early pregnancy risk prediction model for gestational diabetes mellitus. Fetal Diagn Ther. 2019;45:76-84.
  • Borna S, Ashrafzadeh M, Ghaemi M, et al. Correlation between PAPP-A serum levels in the first trimester of pregnancy with the occurrence of gestational diabetes, a multicenter cohort study. BMC Pregnancy Childbirth. 2023;23:847.
  • Gastaldelli A, Gaggini M, DeFronzo RA. Role of adipose tissue insulin resistance in the natural history of type 2 diabetes: results from the San Antonio metabolism study. Diabetes. 2017;66:815-22.
  • Caliskan R, Atis A, Aydin Y, et al. PAPP-A concentrations change in patients with gestational diabetes. Journal of Obstetrics and Gynaecology. 2020;40:190-4.
  • Takele WW, Vesco KK, Josefson J, et al. Effective interventions in preventing gestational diabetes mellitus: a systematic review and meta-analysis. Commun Med (Lond). 2024;4:75.
  • Xiao D, Chenhong W, Yanbin X, et al. Gestational diabetes mellitus and first trimester pregnancy-associated plasma protein A: a case-control study in a Chinese population. J Diabetes Investig. 2018;9:204-10.
  • Ramezani S, Doulabi MA, Saqhafi H, et al. Prediction of gestational diabetes by measuring the levels of pregnancy associated plasma protein-A (PAPP-A) during gestation weeks 11-14. J Reprod Infertil. 2020;21:130-7.
  • Ren Z, Zhe D, Li Z, et al. Study on the correlation and predictive value of serum pregnancy- associated plasma protein A, triglyceride and serum 25-hydroxyvitamin D levels with gestational diabetes mellitus. World J Clin Cases. 2020;8:864-73.
  • Talasaz ZH, Sadeghi R, Askari F, et al. First trimesters pregnancy-associated plasma protein-A levels value to predict gestational diabetes mellitus: a systematic review and meta-analysis of the literature. Taiwan J Obstet Gynecol. 2018;57:181-9.
  • Yanachkova VE, Staynova R, Bochev I, et al. Potential role of biochemical placentation markers - pregnancy associated plasma protein-A and human chorionic gonadotropin for early gestational diabetes screening - a pilot study. Ginekol Pol. 2021 Sep 20. doi: 10.5603/GP.a2021.0129. [Epub ahead of print].
  • Husslein H, Lausegger F, Leipold H, et al. Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11-14 weeks of gestation. J Matern Fetal Neonatal Med. 2012;25:2230-3.
  • Kantomaa T, Vääräsmäki M, Gissler M, et al. First trimester maternal serum PAPP-A and free β-hCG levels and risk of SGA or LGA in women with and without GDM. BMC Pregnancy Childbirth. 2024;24:580.
  • Leung TY, Spencer K, Leung TN, et al. Higher median levels of free β-hCG and PAPP-A in the first trimester of pregnancy in a chinese ethnic group: implication for first trimester combined screening for down’s syndrome in the Chinese population. Fetal Diagn Ther. 2005;21:140-3.
There are 28 citations in total.

Details

Primary Language English
Subjects Obstetrics and Gynaecology
Journal Section Original Articles
Authors

Sema Baki Yıldırım 0000-0001-5321-0739

Neslihan Bezirganoglu Altuntas 0000-0002-6352-4085

Ali Muhtaroğlu 0000-0001-5412-2175

Mehmet Albayrak 0000-0002-2371-6437

Publication Date January 15, 2025
Submission Date December 8, 2024
Acceptance Date January 2, 2025
Published in Issue Year 2025

Cite

AMA Baki Yıldırım S, Bezirganoglu Altuntas N, Muhtaroğlu A, Albayrak M. Can First Trimester Plasma Protein A Level Predict Gestational Diabetes Mellitus. Med Records. January 2025;7(1):240-244. doi:10.37990/medr.1598384

 Chief Editors

Assoc. Prof. Zülal Öner
Address: İzmir Bakırçay University, Department of Anatomy, İzmir, Turkey

Assoc. Prof. Deniz Şenol
Address: Düzce University, Department of Anatomy, Düzce, Turkey

Editors
Assoc. Prof. Serkan Öner
İzmir Bakırçay University, Department of Radiology, İzmir, Türkiye

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