Relationship Between Pregnancy Complications and Serum Pregnancy Associated-Plasma-Protein-A and Free-β-Human Chorionic Gonadotropin in the First Trimester Among Iranian Women
AbstractObjective: To evaluate the relationship between maternal serum levels of pregnancy-associated-plasma-protein-A (PAPP-A) and β-human-chorionic-gonadotropin (β-hCG) and pregnancy complications. Materials and methods: This is a case-control study conducted during 2015- 2016. Women at their first pregnancy were enrolled and serum PAPP-A and free-β-hCG were measured in 9-14 weeks of gestation. They were followed till the end of pregnancylooking for complications including preterm labor, pregnancy induced hypertension (PIH), abortion, and intra-uterine growth retardation (IUGR).Results: A total of 1070 pregnant women (mean age: 28.64 ± 4.95 years) were enrolled. Low serum levels of PAPP-A were more frequent in patients developing IUGR (17.4% versus 1.2%, p < 0.001), preterm labor (13% versus 2%, p = 0.013), and PIH (17.4% versus 4%, p = 0.015) compared those without complications. The serum levels of free-β-hCG were not different in patients with and without complications (p > 0.05). Conclusion: There is an association between low serum levels of PAPP-A and developing IUGR, preterm labor, and PIH.
Ong CY, Liao AW, Spencer K, Munim S, Nicolaides KH. First trimester maternal serum free β human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG 2000;107:1265-70.
Huang S, Chang C, Cheng P, Hsiao C, Soong Y, Duan T. First-Trimester Combined Screening Is Effective for the Detection of Unbalanced Chromosomal Translocations at 11 to 12 Weeks of Gestation. Reprod Sci 2014;21:594-600.
Goetzl L, Krantz D, Simpson JL, Silver RK, Zachary JM, Pergament E, et al. Pregnancy-associated plasma protein A, free β-hCG, nuchal translucency, and risk of pregnancy loss. Obstet Gynecol 2004;104:30-6.
Sharp AN, Alfirevic Z. First trimester screening can predict adverse pregnancy outcomes. Prenat Diagn 2014;34:660-7.
Canini S, Prefumo F, Pastorino D, Crocetti L, Afflitto CG, Venturini PL, et al. Association between birth weight and first-trimester free β–human chorionic gonadotropin and pregnancy-associated plasma protein A. Fertil Steril 2008;89:174-8.
Ranta JK, Raatikainen K, Romppanen J, Pulkki K, Heinonen S. Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption. Eur J Obstet Gynecol Reprod Biol 2011;157:48-52.
Smith GC, Shah I, Crossley JA, Aitken DA, Pell JP, Nelson SM, et al. Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome. Obstet Gynecol 2006;107:161-6.
Savvidou M, Syngelaki A, Muhaisen M, Emelyanenko E, Nicolaides K. First trimester maternal serum free β‐human chorionic gonadotropin and pregnancyassociated plasma protein A in pregnancies complicated by diabetes mellitus. BJOG 2012;119:410-6.
Yaron Y, Heifetz S, Ochshorn Y, Lehavi O, Orr-Urtreger A. Decreased firsttrimester PAPP-A is a predictor of adverse pregnancy outcome. Prenat Diagn 2002;22:778-82.
Cuckle H, Arbuzova S, Spencer K, Crossley J, Barkai G, Krantz D, et al. Frequency and clinical consequences of extremely high maternal serum PAPPA levels. Prenat Diagn 2003;23:385-8.
Kalousova M, Muravska A, Zima T. Pregnancy-associated plasma protein A (PAPP-A) and preeclampsia. Adv Clin Chem 2014;63:169-209.
Wells G, Bleicher K, Han X, McShane M, Chan YF, Bartlett A, et al. Maternal Diabetes, Large-for-Gestational-Age Births, and First Trimester Pregnancy–Associated Plasma Protein-A. J Clin Endocrinol Metab 2015;100:2372-9.
Nese Kavak Z, Basgul A, Elter K, Uygur M, Gokaslan H. The efficacy of first-trimester PAPP-A and free βhCG levels for predicting adverse pregnancy outcome. J Prenat Med 2006;34:145-8.
Tul N, Pusenjak S, Osredkar J, Spencer K, Novak-Antolic Z. Predicting complications of pregnancy with first-trimester maternal serum free-betahCG,PAPP-A and inhibin-A. Prenat Diagn 2003;23:990-6.
Morssink L, Kornman L, Hallahan T, Kloosterman M, Beekhuis J, De Wolf B, et al. Maternal serum levels of free βhCG and PAPPA in the first trimester of pregnancy are not associated with subsequent fetal growth retardation or preterm delivery. Prenat Diagn 1998;18:147-52.
Patil M, Panchanadikar T, 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.
Dugoff L, Hobbins JC, Malone FD, Porter TF, Luthy D, Comstock CH, et al. First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial). Am J Obstet Gynecol2004;191:1446-51.
Meloni P, D'Angeli I, Piazze J, Cerekya A, Simari T, Pala A, et al. First trimester PAPP-A levels associated with early prediction of pregnancy induced hypertension. Hypertens Pregnancy 2009;28:361-8.
Khong T, Wolf Fd, Robertson W, Brosens I. Inadequate maternal vascular response to placentation in pregnancies complicated by preeclampsia and by smallforgestational age infants. Br J Obstet Gynaecol 1986;93:1049-59.
Sonek J, Krantz D, Carmichael J, Downing C, Jessup K, Haidar Z, et al. First trimester screening for early and late preeclampsia using maternal characteristics, biomarkers, and estimated placental volume. Am J Obstet Gynecol 2017.pii: S0002-9378(17)31217-6.
Talmadge K, Vamvakopoulos NC, Fiddes JC. Evolution of the genes for the β subunits of human chorionic gonadotropin and luteinizing hormone. Nature 1984;307:37-40.
Stenman U-H, Tiitinen A, Alfthan H, Valmu L. The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update 2006;12:769-84.
Prior T, Mullins E, Bennett P, Kumar S. Are 1st‐trimester β‐human chorionic gonadotrophin and pregnancyassociated plasma protein A levels predictive of intrapartum fetal compromise in a selected normal population? Aust N Z J Obstet Gynaecol 2014;54:418-23.