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Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening

Published:January 20, 2023DOI:https://doi.org/10.1016/j.ejogrb.2023.01.016

      Highlights

      • High PAPP-A or free β-hCG levels lead to anxiety despite low risk for trisomies.
      • The significance of extremely high PAPP-A or free β-hCG remains unclear.
      • Most pregnancies with extremely increased PAPP-A or free β-hCG have good outcomes.
      • Counselling in patients with extremely high PAPP-A or free β-hCG should be favorable.

      Abstract

      Introduction

      Extreme levels of either PAPP-A or free β-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG.

      Methods

      A total number of 8591 patients with singleton pregnancies between 11 + 0–13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free β-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted.

      Results

      Values of PAPP-A ≥ 2,0 MoM and free β-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free β-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free β-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free β-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free β-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%).

      Discussion

      Pregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free β-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free β-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

      Keywords

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      References

        • Ong C.Y.T.
        • Liao A.W.
        • Spencer K.
        • Munim S.
        • Nicolaides K.H.
        First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications.
        BJOG. 2000; 107: 1265-1270
        • Smith G.C.
        • Stenhouse E.J.
        • Crossley J.A.
        • Aitken D.A.
        • Cameron A.D.
        • Connor J.M.
        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: 1762-1767
        • Shiefa S.
        • Amargandhi M.
        • Bhupendra J.
        • Moulali S.
        • Kristine T.
        First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free beta-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome.
        Indian J Clin Biochem. 2013; 28: 3-12
        • 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: 990-996
        • Bale L.K.
        • Conover C.A.
        Disruption of insulin-like growth factor-II imprinting during embryonic development rescues the dwarf phenotype of mice null for pregnancy-associated plasma protein-A.
        J Endocrinol. 2005; 186: 325-331
        • Gomes M.S.
        • Carlos-Alves M.
        • Trocado V.
        • Arteiro D.
        • Pinheiro P.
        Prediction of adverse pregnancy outcomes by extreme values of first trimester screening markers.
        Obstet Med. 2017; 10: 132-137
        • Giorgetti C.
        • Vanden Meerschaut F.
        • De Roo C.
        • Saunier O.
        • Quarello E.
        • Hairion D.
        • et al.
        Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies.
        Hum Reprod. 2013; 28: 2636-2642
        • Bonne S.
        • Sauleau E.
        • Sananes N.
        • Akaladios C.
        • Rongières C.
        • Pirrello O.
        Influence of medically assisted reproduction techniques on crown-rump length and biochemical markers of trisomy 21 in the first trimester of pregnancy.
        Fertil Steril. 2016; 105: 410-416
        • Szymusik I.
        • Kosinski P.
        • Kosinska-Kaczynska K.
        • Warzecha D.
        • Karwacka A.
        • Kaczynski B.
        • et al.
        The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications.
        J Perinat Med. 2018; 46: 953-959
        • Yigiter A.B.
        • Kavak Z.N.
        • Bakirci N.
        • Gokaslan H.
        Effect of smoking on pregnancy-associated plasma protein A, free beta-human chorionic gonadotropin, and nuchal translucency in the first trimester of pregnancy.
        Adv Ther. 2006; 23: 131-138
        • Dugoff L.
        • Hobbins J.C.
        • Malone F.D.
        • Porter T.F.
        • Luthy D.
        • Comstock C.H.
        • 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: 1446-1451
        • Krantz D.
        • Goetzl L.
        • Simpson J.L.
        • Thom E.
        • Zachary J.
        • Hallahan T.W.
        • 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: 1452-1458
        • Yaron Y.
        • Ochshorn Y.
        • Heifetz S.
        • Lehavi O.
        • Sapir Y.
        • Orr-Urtreger A.
        First trimester maternal serum free human chorionic gonadotropin as a predictor of adverse pregnancy outcome.
        Fetal Diagn Ther. 2002; 17: 352-356
        • Lawrence J.B.
        • Oxvig C.
        • Overgaard M.T.
        • Sottrup-Jensen L.
        • Gleich G.J.
        • Hays L.G.
        • et al.
        The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A.
        Proc Natl Acad Sci U S A. 1999; 96: 3149-3153
        • Turner J.M.
        • Kumar S.
        Low First Trimester Pregnancy-Associated Plasma Protein-A Levels Are Not Associated with an Increased Risk of Intrapartum Fetal Compromise or Adverse Neonatal Outcomes: A Retrospective Cohort Study.
        J Clin Med. 2020; 9: 1108
        • Ziolkowska K.
        • Dydowicz P.
        • Sobkowski M.
        • Tobola-Wrobel K.
        • Wysocka E.
        • Pietryga M.
        The clinical usefulness of biochemical (free beta-hCg, PaPP-a) and ultrasound (nuchal translucency) parameters in prenatal screening of trisomy 21 in the first trimester of pregnancy.
        Ginekol Pol. 2019; 90: 161-166
        • Cuckle H.
        • Arbuzova S.
        • Spencer K.
        • Crossley J.
        • Barkai G.
        • Krantz D.
        • et al.
        Frequency and clinical consequences of extremely high maternal serum PAPP-A levels.
        Prenat Diagn. 2003; 23: 385-388