The role of pregnancy-associated plasma protein-a level in the first trimester of pregnancy and clinical outcome in an urban referral centre

Lavanya T., Premalatha R., Nandita A. Thakkar, Latha Jawahar, Priya Kannappa Rajendran, Geethanjali E., Swetha V. Rajan


Background: Estimation of serum PAPP-A levels studied predictability for adverse perinatal outcome. This case control study tries to establish the association between low PAPP-A levels among the pregnant woman and adverse maternal foetal outcome.

Methods: This is an case-control study during 2017-2018 in the women delivered at Department of OBG at Mehta Hospitals. Women delivered in the labour room  had a first trimester screening of PAPP-A level were explained, taken informed consent, questionnaire which include detailed antenatal history, mode of delivery and baby data.  Depending upon outcome, the subjects are classified as case group or control group, out of the study sample of 264 subjects, 88 patients who had complications were taken as cases and 176 patients with no complications taken as control were undertaken.

Results: Low PAPP-A level (<0.5 MoM) showed high incidence of PIH and preeclampsia, followed by IUGR and Preterm. PAPP-A level >0.5 MoM, normal outcome is more than the adverse outcome. The difference in the PAPP-A levels is statistically significant. In women with low PAPP A level, low birth weight found statistically significant when compared with <0.5 PAPP A level. The sensitivity of PAPP A levels in identifying the complicated outcomes was 17.04%.The specificity was 98.85%. The positive predictive value of predicting the complications was 88.23% and negative predictive value of 70.44%.

Conclusions: The low PAPP-A levels confirmed during first trimester of pregnancy is associated with adverse maternal and foetal outcome such as PIH, preeclampsia, preterm, IUGR and LBW.


Free beta HCG, IUGR, NT, PAPP-A, Preterm labour, Preeclampsia

Full Text:



Gude NM, Roberts CT, Kalionis B, King RG. Growth and function of the normal human placenta. Thromb Res. 2004;114(5-6):397-407.

Garnica AD, Chan WY. The role of the placenta in fetal nutrition and growth. J Am Coll Nutr. 1996;15(3):206-22.

Hay WW. Placental transport of nutrients to the fetus. Horm Res. 1994;42(4-5):215-22.

Gagnon A, Wilson RD, Audibert F. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008;30:918-49.

Goetzl L. Adverse pregnancy outcomes after abnormal first-trimester screening for aneuploidy. Clin Lab Med. 2010;30(3):613-28.

Saruhan Z, Ozekinci M, Simsek M, Mendilcioglu I. Association of first trimester low PAPP-A with adverse pregnancy outcomes. Clin Exp Obstet Gynecol. 2012;39(2):225-8.

Spencer CA, Allen VM, Flowerdew G, Dooley K, Dodds L. Low levels of maternal serum PAPP‐A in early pregnancy and the risk of adverse outcomes. Prenat Diagn. 2008;28(11):1029-36.

Yaron Y, Heifetz S, Ochshorn Y, Lehavi O, Orr-Urtreger A. Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome. Prenat Diagn. 2002;22:778-82.

Scott F, Coates A, McLennan A. Pregnancy outcome in the setting of extremely low first trimester PAPP-A levels. Aust NZJ Obstet Gynaecol. 2009;49:258-62.

Marttala J, Peuhkurinen S, Laitinen P, Gissler M, Nieminen P, Ryynanen M. Low maternal PAPP‐A is associated with small‐for‐gestational age newborns and stillbirths. Acta Obstet Gynecol Scand. 2010;89(9):1226-8.

Kirkegaard I, Uldbjerg N, Henriksen TB. PAPP-A and free β-hCG in relation to admission to neonatal intensive care unit and neonatal disease. Prenat Diagn. 2011;31:1169-75.

Carbone JF, Tuuli MG, Bradshaw R, Liebsch J, Odibo AO. Efficiency of first‐trimester growth restriction and low pregnancy‐associated plasma protein‐A in predicting small for gestational age at delivery. Prenat Diagn. 2012;32(8):724-9.

Fox NS, Chasen ST. First trimester pregnancy associated plasma protein - A as a marker for poor pregnancy outcome in patients with early-onset fetal growth restriction. Prenat Diagn. 2009;29:1244-8.

Peterson SE, Simhan HN. First-trimester pregnancy-associated plasma protein A and subsequent abnormalities of fetal growth. Am J Obstet Gynecol. 2008;198(5):43-5.

Pummara P, Tongsong T, Wanapirak C, Sirichotiyakul S, Luewan S. Association of first-trimester pregnancy-associated plasma protein A levels and idiopathic preterm delivery: A population-based screening study. J Obstet Gynaecol. 2016;55:72-5.

Bell AW, Hay WW, Ehrhardt RA. Placental transport of nutrients and its implications for fetal growth. J Reprod Fertil Suppl. 1999;54:401-10.

Costa MA. The endocrine function of human placenta: an overview. Reprod Biomed Online. 2016;32(1):14-43.

Mesdaghinia E, Behrashi M, Saeidi A, Kalahroodi MA, Sehat M. Association between PAPP-A and placental thickness. Int J Reprod Bio Med. 2016;14(6):421-6.

Proctor LK, Toal M, Keating S, Chitayat D, Okun N, Windrim RC, Smith GC, Kingdom JC. Placental size and the prediction of severe early‐onset intrauterine growth restriction in women with low pregnancy‐associated plasma protein‐A. Ultrasound Obstet Gynaecol. 2009;34(3):274-82.

Chakraborty C, Gleeson LM, McKinnon T, Lala PK. Regulation of human trophoblast migration and invasiveness. Can J Physiol Pharmacol. 2002;80(2):116-24.

Kaufmann P, Black S, Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod. 2003;69(1):1-7.

Brameld KJ, Dickinson JE, O'Leary P, Bower C, Goldblatt J, Hewitt B, Murch A, Stock R. First trimester predictors of adverse pregnancy outcomes. Aust NZJ Obstet Gynaecol. 2008;48:529-35.

Ravenswaaij VR, Goot TM, Wolf S, Spruijt LM, Visser GH, Schielen PC. First trimester serum PAPP-A and fβ-hCG concentrations and other maternal characteristics to establish logistic regression based predictive rules for adverse pregnancy outcome. Prenat Diagn. 2011;31:50-7.

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;31:147-52.

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;31:15-19.

Spencer K, Cowans NJ, Avgidou K, Nicolaides KH. Firsttrimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death. Ultrasound Obstet Gynecol. 2006;28:637-43.

Kuc S, Wortelboer EJ, Rijn BB, Franx A, Visser GH, Schielen PC. Evaluation of 7 serum biomarkers and uterine artery Doppler ultrasound for first-trimester prediction of preeclampsia: a systematic review. Obstet Gynecol Surv. 2011;66(4):225-39.

Bilagi A, Burke DL, Riley RD, Mills I, Kilby MD, Morris KR. Association of maternal serum PAPP-A levels, nuchal translucency and crown-rump length in first trimester with adverse pregnancy outcomes: retrospective cohort study. Prenat Diagn. 2017;37(7):705-11.

Gagnon A, Wilson RD, Audibert F. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008;30:918-49.

Krantz D, Goetzl L, Simpson JL, Thom E, Zachary J, Hallahan TW, et al. Association of extreme first-trimester free human chorionic gonadotropin beta,pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes. Am J Obstet Gynecol. 2004;191:1452-8.

Dugoff L. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes. Obstet Gynecol. 2010;115(5):1052-61.

Kavak ZN, Basgul A, Elter K, Uygur M, Gokaslan H. The efficacy of first-trimester PAPP-A and free beta hCG levels for predicting adverse pregnancy outcome. J Perinat Med. 2006;34:145-8.

Mithil P, Panchanadikar TM, Girija W. Variation of Papp-A level in the first trimester of pregnancy and its clinical outcome. J Obstet Gynecol India. 2014;64(2):116-9.

Gagnon A, Wilson RD, Audibert F, Allen VM, Blight C, Brock JA, et al. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008;30(10):918-32.

Halscott TL, Ramsey PS, Reddy UM. First trimester screening cannot predict adverse outcomes yet. Prenat Diagn. 2014;34(7):668-76.

Morssink LP, Kornman LH, Hallahan TW, Kloosterman MD, Beekhuis JR, Wolf BT, et al. Maternal serum levels of free beta-hCG and PAPP-A in the first trimester of pregnancy are not associated with subsequent fetal growth retardation or preterm delivery. Prenat Diagn.1998;18(2):147-52.

Leung TY, Chan LW, Leung TN, Fung TY, Sahota DS, Lau TK. First-trimester maternal serum levels of placental hormones are independent predictors of second-trimester fetal growth parameters. Ultrasound Obstet Gynecol. 2006;27:156-61.

Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early pregnancy levels of pregnancy associated plasma protein A and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab. 2002;87:1762-7.

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 Gynecol. 2004;191:1446-51.

Malik J, Rai P, Das A, Das S. Pregnancy - associated plasma protein A - a level in first trimester and its impact on pregnancy outcome. Br J Obstet Gynaecol. 2016;5(8):2680-3.