Association of serum pregnancy associated plasma protein: a with gestational diabetes mellitus


  • Khadiza Begum Department of Fetomaternal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
  • Mousumi Saha Department of Fetomaternal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
  • Jesika Rizvi Tamanna Department of Gynecology and Obstetrics, Bangabandhu Sheikh Mujib Medical College and Hospital (BBSMMCH), Faridpur, Bangladesh
  • Ferdous Ara Banu Department of Fetomaternal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
  • Sharmin Ferdous Department of Fetomaternal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
  • A. K. M. Mizanur Rahman CMH, Dhaka, Bangladesh
  • Nahreen Akhtar Department of Fetomaternal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh



Gestational diabetes mellitus, Insulin like growth factor, Insulin like growth factor binding protein, Pregnancy associated plasma protein A


Background: Gestational diabetes mellitus is defined as diabetes diagnosed during pregnancy that is not clearly overt diabetes. GDM has many adverse consequences on the health of mother and fetus.

Methods: This cohort study was carried out involving 77 women of 11 to14-week pregnant attending in the Gynecology & Obstetrics and Fetomaternal Medicine OPD, BSMMU from September 2020 to August 2021.

Results: Respondents were divided into two groups. Low PAPP-A group (<0.5MoM) and normal PAPP-A group (>0.5MoM). In low PAPP-A group, out of 16 respondents, 8 (42.1%) developed GDM and remaining 8(13.8%) were euglycemic. Whereas, in normal PAPP-A group, out of 61 respondents, majority 50 (86.2%) were euglycemic and only 11 (57.9%) women developed GDM. A total 19 (24.68%) respondents developed GDM from both low and normal PAPP-A group. ROC analysis of PAPP-A level for detection of GDM, a AUC value of 0.889 (95% CI 0.818-0.960) found which was statistically significant. A cut off value of ≤16.80 showed the highest Youden index (0.652) with 89.4% sensitivity and 81% specificity, the accuracy was 83.35. Moreover, a cut off value ≤16.80 showed PPV and NPV of 62.1% and 95.9%, respectively. PAPP-A level of GDM detected (10.32±5.56) µg/ml was significantly lower from non GDM mothers (25.08 ±9.85) µg/ml, where p<0. 001.

Conclusions: Study finding revealed that maternal serum PAPP-A level was lower in 11-14 weeks of pregnancy who subsequently developed GDM. So, a low PAPP-A level (<0.5 MoM) in 11-14 weeks of pregnancy is associated for development of GDM.


Mohiuddin AK. Diabetes fact: Bangladesh perspective. Inter j diab res. 2019;2(l):14-20.

Imoh LC, Asorose AS, Odo AI, Aina DO, Abu AO, Ocheke AN. Modification of WHO diagnostic criteria for gestational diabetes: implications for classification of hyperglycemia in pregnancy. Int J Reprod Contracept Obstet Gynecol. 2017;6:2716-23.

Carr DB, Gabbe S. Gestational diabetes: detection, management, and implications. Clin Diabet. 1998;16(1):4-12.

Creasy RK, Resnik R, Lams JD, Lockwood, Moore TR, Greene MF. Maternal-fetal medicine principle and practice. 7th ed. Philadelphia: Elsevier Saunders; 2014.

Harlev A, Agarwal A, Esteves SC. Cigarette smoking and semen quality: a new meta-analysis examining the effect of the 2010 world health organization laboratory methods for the examination of human semen. Eur Urol. 2016;70(4):635-645.

Berberoglu Z. Pathophysiology of gestational diabetes mellitus. EMJ Diabet. 2019;7(1):97-106.

Beneventi F, Simonetta M, Locatelli E, Cavagnoli C, Badulli C, Lovati E, et al. Temporal variation in soluble human leukocyte antigen‐G (sHLA‐G) and pregnancy‐associated plasma protein A (PAPP‐A) in pregnancies complicated by gestational diabetes mellitus and in controls. Ame J Reprod Immunol. 2014;72(4):413-21.

Jarmuzek P, Wielgos M, Bomba-Opon D. Placental pathologic changes in gestational diabetes mellitus. Neuroendocrinol Lett. 2015;36(2):101-5.

Huynh DT, Devitt AA, Paule CL, Reddy BR, Marathe P, Hegazi RA, et al. Effects of oral nutritional supplementation in the management of malnutrition in hospital and post-hospital discharged patients in India: a randomised, open-label, controlled trial. J Hum Nutr Diet. 2015;28(4):331-43.

Ramezani S, Doulabi MA, Saqhafi H, Alipoor M. Prediction of gestational diabetes by measuring the levels of pregnancy associated plasma protein-A (PAPP-A) during gestation weeks 11–14. J Reproduct Infertil. 2020;21(2):130.

Mansell W, McEvoy P, Tai S. What is good communication for people living with dementia? A mixed-methods systematic review. Int Psychogeriatr. 2017;29(11):1785-1800.

Lamain-de Ruiter M, Kwee A, Naaktgeboren C A, de Groot I, Evers I M, Groenendaal F, et al. External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study. BMJ. 2016;354:i4338.

Dudzińska M, Tarach JS, Matuszek B, Kowalczyk M, Wdowiak-Barton B, Kiszczak-Bochyńska E, et al. Evaluation of metabolic control in patients with type 2 diabetes depending on the type of hypoglycemic treatment. Experim Clin Diabetol/Diabetol Doswiadcz Klini. 2011;11(1).

Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J (Engl). 2020;133(9):1015-24.

Fruscalzo A, Cividino A, Rossetti E, Maurigh A, Londero AP, Driul L. First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring. Scientific Reports. 2020;10(1):5131.

Farina M, Rocha JB, Aschner M. Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies. Life Sci. 2011;89(15-16):555-63.

Wright D, Silva M, Papadopoulos S, Wright A, Nicolaides KH. Serum pregnancy‐associated plasma protein‐A in the three trimesters of pregnancy: effects of maternal characteristics and medical history. Ultrasound Obst Gynecol. 2015;46(1):42-50.

Ledesma J. Conceptual frameworks and research models on resilience in leadership. Sage open. 2014;4(3):2158244014545464.

Martin S, Ferraz T, Pinto P, Guianas JT, Montenegro N, Ramalho C. Serum PAPPA as a predictor of gestational diabetes. Ame J Obstrt Gynecol. 2015;212(l):366-7.

Khalil S, Bardawil T, Stephan C, Darwiche N, Abbas O, Kibbi AG, et al. Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects. J Dermatolog Treat. 2017;28(8):684-696.

Yen I-W, Lee C-N, Lin M-W, Fan K-C, Wei J-N, Chen K-Y, et al. Overweight and obesity are associated with clustering of metabolic risk factors in early pregnancy and the risk of GDM. PLoS ONE 2019;14(12):e0225978.

Cosson A, Chapiro E, Bougacha N, Lambert J, Herbi L, Cung HA, et al. Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1. Leukemia. 2017;31(7):1625-1629.

Kirkegaard H, Johnsen NF, Christensen J, Frederiksen K, Overvad K, Tjønneland A. Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study. BMJ. 2010;341:c5504.

Inan OT, Baran Pouyan M, Javaid AQ, Dowling S, Etemadi M, Dorier A, et al. Novel wearable seismocardiography and machine learning algorithms can assess clinical status of heart failure patients. Circ Heart Fail. 2018;11(1):e004313.

Sweeting AN, Wong J, Appelblom H, Ross GP, Kouru H, Williams PF, et al. A first trimester prediction model for gestational diabetes utilizing aneuploidy and pre-eclampsia screening markers. J Mater-Fet Neonat Medi. 2018;31(16):2122-30.

Donovan RJ, Rossiter JR, Marcoolyn G, Nesdale A. Store atmosphere and purchasing behavior. J Retaili. 1994;70(3):283-94.

Shah K, Sultana R, Bhat R, Bhat P, Bhat S. Impact of high levels of pregnancy associated plasma protein-a on pregnancy. J Clin Diagnos Res. 2018;12(9).

Ramezani S, Doulabi MA, Saqhafi H, Alipoor M. 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(2):130-7.

Husslein H, Lausegger F, Leipold H, Worda C. Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11–14 weeks of gestation. J Mat-Fetal Neonat Medi. 2012;25(11):2230-3.






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