Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Prediction of Gestational Diabetes by Measuring the Levels of Pregnancy Associated Plasma Protein-A (PAPP-A) During Gestation Weeks 11-14

Authors
Somayeh Ramezani 1
Mahboubeh Ahmadi Doulabi 2
Hamid Saqhafi 3
Mahmood Alipoor 4
1 Student Research Committee, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Midwifery and Reproductive Health Research Center, Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 School of Paramedical Sciences, Qazvin University of Medical Sciences, Qazvin, Iran
4 Department of Biostatistics, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Abstract
Background: The present study aimed to determine the association between pregnancy-associated plasma protein A (PAPP-A) and Gestational Diabetes Methods (GDM) to detect a risk factor for predicting GDM at gestational weeks 11-14. Methods: This analytical prospective study recruited 284 pregnant women presenting to six healthcare centers of Qazvin, Iran from February to December 2016. PAPP-A was measured at gestational weeks 11-14 and glucose tolerance test was conducted at gestational weeks 24-28. The participants were assigned into two groups of exposure (reduced PAPP-A) and non-exposure (normal PAPP-A). The association between GDM and PAPP-A was studied. The number of women in exposure group were 201 and 83 in the non-exposure group. Differences between groups were assessed by the Mann–Whitney, Chi-square, T test, logistic regression analysis and ROC Curve with a significance level of 0.05. Results: Twenty eight (33.73%) patients of the exposure group and 17 (8.46%) of non-exposure group developed GDM. There was a significant difference between the two groups in terms of GDM (p<0.001) and the risk of GDM was 3.98 fold higher in the exposure group (reduced PAPPA mu/L) than that of the non-exposure group (CI=2.39-6.65, p<0.001). Also, 53.3% of the exposure group and 46.7% of the non-exposure group were diagnosed with GDM (p=0.02). There was a significant difference in GDM between the groups and the risk of GDM was 1.85 times higher in the exposure group (reduced PAPPA MOM) than that in the control group (CI=1.09-3.15, p=0.020). According to the ROC curve results, PAPP-A and MOM are acceptable indicators for predicting GDM. Conclusion: A low PAPP-A level (MOM, MU/L) as a new risk factor for GDM can help early prediction and prevent maternal and fetal complication by timely treatment.
Keywords
Gestational diabetes
pregnancies
Pregnancy associated plasma protein A
  1. American diabetes association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl 1):S8-16.
  2. Bloom SL, Corton MM, Spong CY, Dashe JS, Leveno KJ. Williams Obstetrics. 24 ed. USA: McGraw Hill education; 2014. 1376 p.
  3. del Rosario-Capellan ML, Carlos-Raboca J, Litonjua AD. Total sialic acid and other inflammatory markers as predictors of gestational diabetes. Philos J Intern Med. 2009;47:11-7.
  4. Baptiste-Roberts K, Barone BB, Gary TL, Golden SH, Wilson LM, Bass EB, et al. Risk factors for type 2 diabetes among women with gestational diabetes: a systematic review. Am J Med. 2009;122(3): 207-14.e4.
  5. Ahi Z, Kariman N, Zahedi S, Shakeri N. Relationship between maternal serum C-reactive protein concentration and gestational diabetes mellitus. Adv Nurs Midwifery. 2015;24(85):31-8.
  6. Reece EA. The fetal and maternal consequences of gestational diabetes mellitus. J Matern Fetal Neonatal Med. 2010;23(3):199-203.
  7. Coustan DR, Lowe LP, Metzger BE, Dyer AR, International association of diabetes and pregnancy study groups. The hyperglycemia and adverse pregnancy outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus. Am J Obstet Gynecol. 2010;202(6):654-e1-6.
  8. Kampmann U, Madsen LR, Skajaa GO, Iversen DS, Moeller N, Ovesen P. Gestational diabetes: a clinical update. World J Diabetes. 2015;6(8):1065-72.
  9. Vild As. Screening in obstetrics and gaynocology disease. Zahrani F, Behbahani B, Tehrani T. qhom: Fanose Roshan; 2011.
  10. Protocol of screening and diagnosis of gestational diabetes [internet]. 2013[cited2016 october 6]: [about 3 p.].available from health .behdasht.gov.ir
  11. Inan C, Varol FG, Erzincan SG, Uzun I, Sutcu H, Sayin NC. Use of prokineticin-1 (PROK1), pregnancy-associated plasma protein A (PAPP-A) and PROK1/PAPP-A ratio to predict adverse pregnancy outcomes in the first trimester: a prospective study. J Matern Fetal Neonatal Med. 2018;31(20):2685-92.
  12. Beneventi F, Simonetta M, Lovati E, Albonico G, Tinelli C, Locatelli E, et al. First trimester pregnancy‐associated plasma protein‐A in pregnancies complicated by subsequent gestational diabetes. Prenat Diagn. 2011;31(6):523-8.
  13. 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. Am J Reprod Immunol. 2014;72(4):413-21.
  14. Huynh L, Kingdom J, Akhtar S. Low pregnancy-associated plasma protein A level in the first trimester. Can Fam Physician. 2014;60(10):899-903.
  15. Lovati E, Beneventi F, Simonetta M, Laneri M, Quarleri L, Scudeller L, et al. Gestational diabetes mellitus: including serum pregnancy-associated plasma protein-A testing in the clinical management of primiparous women? a case–control study. Diabetes Res Clin Pract. 2013;100(3):340-7.
  16. Giudice I, Benintende G, Di Nicolò AM, Mangiameli D, Carrara G, Randazzo C, et al. Correlation of neonatal weight with maternal serum levels of pregnancy-associated plasma protein-A during the first trimester of pregnancy: a retrospective study. J Perinat Med. 2015;43(2):227-32.
  17. Ledesma AM, Yuste MG, Bújez AR, et al. Low Maternal Serum PAPP-A Levels in the First Trimester of Gestation and the Risk of Gestational Diabetes. In18th world congresson controversies in obstetrics obstetric, gynecology & infertility (COGI) 2014 (p. 183).
  18. Schaas C, Titianu M, Visinari R, Berescu A, Carp A, Onofriescu M. PAPP‐A—a marker for gestational diabetes? Ultrasound Obstet Gynecol. 2012;40(S1):192.
  19. 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 Matern Fetal Neonatal Med. 2012;25(11):2230-3.
  20. Spencer K, Cicero S, Atzei A, Otigbah C, Nicolai-des KH. The influence of maternal insulin‐de-pendent diabetes on fetal nuchal translucency thickness and first‐trimester maternal serum biochemical markers of aneuploidy. Prenat Diagn. 2005;25(10):927-9.
  21. Jelliffe-Pawlowski LL, Baer RJ, Currier RJ, Lyell DJ, Blumenfeld YJ, El-Sayed YY, et al. Early-onset severe preeclampsia by first trimester pregnancy-associated plasma protein A and total human chorionic gonadotropin. Am J Perinatol. 2015; 32(07):703-12.
  22. Spencer K, Cowans NJ, Avgidou K, Molina F, Nicolaides KH. First‐trimester biochemical markers of aneuploidy and the prediction of small‐for‐ gestational age fetuses. Ultrasound Obstet Gynecol. 2008;31(1):15-9.
  23. Spencer K, Cowans NJ, Molina F, Kagan KO, Nicolaides KH. First‐trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery. Ultrasound Obstet Gynecol. 2008;31(2):147-52.
  24. Ong CY, Liao AW, Spencer K, Munim S, Nicolaides KH. First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG. 2000;107(10):1265-70.
  25. Iversen KK, Dalsgaard M, Teisner AS, Schoos M, Teisner B, Nielsen H, et al. Pregnancy-associated plasma protein-A, a marker for outcome in patients suspected for acute coronary syndrome. Clin Biochem. 2010;43(10):851-7.
  26. Sweeting AN, Wong J, Appelblom H, Ross GP, Kouru H, Williams PF, et al. A novel early pregnancy risk prediction model for gestational diabetes mellitus. Fetal Diagn Ther. 2019;45(2):76-84.
  27. Donovan BM, Nidey NL, Jasper EA, Robinson JG, Bao W, Saftlas AF, et al. First trimester prenatal screening biomarkers and gestational diabetes mellitus: A systematic review and meta-analysis. PloS one. 2018;13(7):e0201319.
  28. Shah K, Sultana R, Bhat R, Bhat P, Bhat S. Impact of high levels of pregnancy associated plasma protein-A on pregnancy. J Clin Diagn Res. 2018;12 (9):9-13.
  29. Sweeting AN, Wong J, Appelblom H, Ross GP, Kouru H, Williams PF, et al. A first trimester pre-diction model for gestational diabetes utilizing aneuploidy and pre-eclampsia screening markers. J Matern Fetal Neonatal Med. 2018;31(16):2122-30.
  30. Ramezani S, Ahmadi M, Saghafi H, Alipoor M. Association of pregnancy association plasma protein A (PAPP-A) and gestational diabetes. Iran J Obstet Gynecol Infertil. 2017;20(1):61-9.
  31. Maymon R, Meiri H, Svirski R, Weiner E, Cuckle H. Maternal serum screening marker levels in twin pregnancies affected by gestational diabetes. Arch Gynecol Obstet. 2019;299(3):655-63.
  32. Xiao D, Chenhong W, Yanbin X, Lu Z. Gestational diabetes mellitus and first trimester pregnancy-associated plasma protein A: a case–control study in a Chinese population. J Diabets Investig. 2018;9 (1):204-10.
  33. Pellitero S, Reverter JL, Pizarro E, Pastor MC, Granada ML, Tàssies D, et al. Pregnancy-associated plasma protein-a levels are related to glycemic control but not to lipid profile or hemostatic parameters in type 2 diabetes. Diabetes Care. 2007;30 (12):3083-5.
  34. Savvidou MD, Syngelaki A, Muhaisen M, Emelyanenko E, Nicolaides KH. First trimester maternal serum free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein A in pregnancies complicated by diabetes mellitus. BJOG. 2012;119(4):410-6.
  35. Nanda S, Savvidou M, Syngelaki A, Akolekar R, Nicolaides KH. Prediction of gestational diabetes mellitus by maternal factors and biomarkers at 11 to 13 weeks. Prenat Diagn. 2011;31(2):135-41.
  36. Teede HJ, Harrison CL, Teh WT, Paul E, Allan CA. Gestational diabetes: development of an early risk prediction tool to facilitate opportunities for prevention. Aust N Z J Obstet Gynaecol. 2011;51 (6):499-504.
Journal of Reproduction & Infertility
Volume 21, Issue 2
Spring 2020
Pages 130-137