Maternal serum screening marker levels in twin pregnancies affected by gestational diabetes
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To investigate the levels of maternal serum screening markers in the first and second trimester twin pregnancies, which subsequently developed gestational diabetes mellitus (GDM).
145 twin pregnancies were recruited in the first trimester. Stored blood samples were retrospectively tested for pregnancy-associated plasma protein (PAPP)-A, human chorionic gonadotrophin (hCG), placental growth factor (PlGF), placental protein (PP)13, α-fetoprotein (aFP) and inhibin A. Values were expressed in multiples of the gestation-specific median (MoMs) in singletons, adjusted for maternal weight and parity, as appropriate.
Twenty samples of first and second trimester were available from 11 twins who subsequently developed GDM and 219 samples from unaffected twins. The median PAPP-A level in the affected twins was 3.61 MoM compared with 2.46 MoM in unaffected twins (P < 0.001, Wilcoxon rank sum test, two tailed); significant results were found in both trimesters. The median PP13 was also increased but to a lesser extent. It was only statistically significant overall (P < 0.05) and in second trimester samples (P < 0.02). No other marker differed significantly. Logistic regression found that combining PAPP-A and maternal weight had a 55% detection rate for a 10% false-positive rate.
Early prenatal marker evaluation in twin pregnancies can be also useful for predicting the risk for developing GDM and should be further investigated.
KeywordsScreening Maternal serum biomarkers Gestational diabetes Twins PAPP-A PP13
RM: clinical protocol and project development, data management, data analysis, manuscript writing and editing. HM: clinical protocol development, data analysis, manuscript writing and editing, and others—test biomarkers. RS: protocol development, data collection and management, data analysis, and manuscript writing. EW: data analysis and manuscript writing. HC: project development, data analysis, manuscript writing and editing
Partial support from ASPRE FP7 # 601852 grant (HM), Institute of Ultrasound in Obstetrics and Gynecology, The Yitzhak Shamir Medical Center (formerly Assaf Harofeh Medical Center) (RM) and PerkinElmer Inc.
Compliance with ethical standards
Conflict of interest
Howard Cuckle is a consultant to PerkinElmer Inc. Hamutal Meiri holds partial patent rights for placental protein 13. Ron Maymon, Ran Svirski, and Eran Weiner have no conflicts of interest to declare. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Upon recruitment to the study, all women signed an informed consent and the study received our institutional ethical review board permission #217/13.
- 1.Hod M, Kapur A, Sacks DA, Hadar E, Agarwal M, Di Renzo GC, Cabero Roura L, McIntyre HD, Morris JL, Divakar H (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–S211. https://doi.org/10.1016/s0020-7292(15)30007-2 CrossRefPubMedGoogle Scholar
- 2.Sacks DA, Hadden DR, Maresh M, Deerochanawong C, Dyer AR, Metzger BE, Lowe LP, Coustan DR, Hod M, Oats JJ, Persson B, Trimble ER, HAPO Study Cooperative Research Group (2012) Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel-recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Diabetes Care 35(3):526–528. https://doi.org/10.2337/dc11-1641 CrossRefPubMedPubMedCentralGoogle Scholar
- 3.American Diabetes Association (2003) Gestational diabetes mellitus. Diabetes Care 26(Suppl 1):S103–S105Google Scholar
- 5.Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, Wapner RJ, Varner MW, Rouse DJ, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Lain KY, Sorokin Y, Peaceman AM, Tolosa JE, Anderson GB, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network (2009) A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 361:1339–1348. https://doi.org/10.1056/NEJMoa0902430 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva Ad, Hod M, Kitzmiler JL, Lowe LP, McIntyre HD, Oats JJ, Omori Y, Schmidt MI, International Association of Diabetes and Pregnancy Study Groups consensus panel (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33:676–682. https://doi.org/10.2337/dc09-1848 CrossRefPubMedGoogle Scholar
- 8.Arabin B, Baschat AA (2017) Pregnancy: an underutilized window of opportunity to improve long-term maternal and infant health-an appeal for continuous family care and interdisciplinary communication. Front Pediatr 5:69. https://doi.org/10.3389/fped.2017.00069.eCollection2017 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Savvidou MD, Syngelaki A, Muhaisen M, Emelyanenko E, Nicolaides KH (2012) First trimester maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus. BJOG 119(4):410–416. https://doi.org/10.1111/j.1471-0528.2011.03253.x CrossRefPubMedGoogle Scholar
- 13.Husslein H, Lausegger F, Leipold H, Worda C (2012) Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11–14 weeks of gestation. J Matern Fetal Neonatal Med 25(11):2230–2233. https://doi.org/10.3109/14767058.2012.684170 CrossRefPubMedGoogle Scholar
- 14.Lovati E, Beneventi F, Simonetta M, Laneri M, Quarleri L, Scudeller L, Albonico G, Locatelli E, Cavagnoli C, Tinelli C, Spinillo A, Corazza GR (2013) 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 100(3):340–347. https://doi.org/10.1016/j.diabres.2013.04.002 CrossRefPubMedGoogle Scholar
- 17.Beneventi F, Simonetta M, Locatelli E, Cavagnoli C, Badulli C, Lovati E, Garbin G, Genini E, Albertini R, Tinelli C, Martinetti M, Spinillo A (2014) 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 72(4):413–421. https://doi.org/10.1111/aji.12270 CrossRefPubMedGoogle Scholar
- 18.Wells G, Bleicher K, Han X, McShane M, Chan YF, Bartlett A, White C, Lau SM (2015) Maternal diabetes, large-for-gestational-age births, and first trimester pregnancy-associated plasma protein-A. J Clin Endocrinol Metab 100(6):2372–2379. https://doi.org/10.1210/jc.2014-4103 CrossRefPubMedGoogle Scholar
- 27.Maymon R, Trahtenherts A, Svirsky R, Melcer Y, Madar-Shapiro L, Klog E, Meiri H, Cuckle H (2017) Developing a new algorithm for first and second trimester pre-eclampsia screening in twins pregnancies. Hypertens Pregnancy 36(1):108–115. https://doi.org/10.1080/10641955.2016.1242605 CrossRefPubMedGoogle Scholar
- 29.Committee on Practice Bulletins—Obstetrics (2013) Practice Bulletin No. 137: gestational diabetes mellitus. Obstet Gynecol 122(2 Pt 1):406–416. https://doi.org/10.1097/01.AOG.0000433006.09219.f1 CrossRefGoogle Scholar
- 30.Hod M, Kapur A, Sacks DA, Hadar E, Agarwal M, Di Renzo GC, Cabero Roura L, McIntyre HD, Morris JL, Divakar H (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–S211. https://doi.org/10.1016/S0020-7292(15)30007-2 CrossRefPubMedGoogle Scholar
- 31.Madhuvrata P, Govinden Gemma, Bustani R, Song S, Farrell TA (2015) Prevention of gestational diabetes in pregnant women with risk factors for gestational diabetes: a systematic review and meta-analysis of randomised trials. Obstet Med 8(2):68–85. https://doi.org/10.1177/1753495X15576673 CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Drobnjak T, Gizurarson S, Gokina NI, Meiri H, Mandalá M, Huppertz B, Osol G (2017) Placental protein 13 (PP13)-induced vasodilation in pregnant and non-pregnant rat arteries occurs via endothelial signaling pathways. Hypertens Pregnancy 36(3):186–195. https://doi.org/10.1080/10641955.2017.1295052 CrossRefPubMedGoogle Scholar