Pregnancy-associated Plasma Protein A Levels with Pregnancy Outcomes: A preliminary study

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Indu Lata
Prabhakar Mishra

Abstract

Objectives: In the first trimester serum screening pregnancy-associated plasma protein-A (PAPP-A) levels are estimated in pregnant women. Its low values are leading to more risk of preterm delivery, isolated intrauterine growth restriction (IUGR), intrauterine death (IUD) or neonatal death, pregnancy-induced hypertension (PIH), and intrahepatic cholestasis of pregnancy (IHCP). The objective of this study was to find the correlation of PAPP-A levels with pregnancy outcomes and complications.
Materials and Methods: This retrospective study was done on the patients visiting the antenatal outpatient department for first trimester screening (11-13 weeks). Ultrasonographic nuchal translucency scan and blood sample test for double marker were performed. Based on the multiple of median (MOM) value of PAPP-A, two groups were made. MOM value ≥ 0.5 (normal PAPP-A levels) was considered as the control group and MOM value < 0.5 (low PAPP-A levels) was considered as the study group. Data were collected and analyzed. Pregnant women were followed-up until delivery. Pregnancy outcomes and complications were recorded.
Results: A total of 141 patients qualified and included in the study, 126 patients had normal (control group) and 15 had low PAPP-A values (study group). The study group had significant higher complications when compared to control group as IHCP (46.6% vs 14.3%, p = 0.002), IUGR (26.6% vs 8.7%, p = 0.034), preterm delivery (46.67% vs 19.84%, p = 0.017), IUD (13.3% vs 0.79%, p = 0.001) and fetal distress (13.3% vs 1.58%, p = 0.009). The patients of study group having more gestational diabetes (20% vs 16.6%, p = 0.744), both PIH and oligohydramnios (13.3% vs 7.93%, p = 0.482) and premature rupture of membranes (6.66% vs 0.79%, p = 0.069) that were insignificantly higher as compared to control groups.
Conclusion: The PAPP-A levels measurement is a valuable marker during the first -trimester screening for predicting adverse outcomes and complications, as low PAPP-A level was associated with a high chance of preterm delivery, IUGR, IHCP, and adverse fetal outcome.

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References

1. Shiefa S, Amargandhi M, Bhupendra J, Moulali S, Kristine T. First trimester taternal serum screening using biochemical markers PAPP-A and free β-hCG for Down syndrome, Patau syndrome and Edward syndrome. Indian J Clin Biochem 2013;28:3-12.
2. Zhang Z, Xu H, Liu X, Li P, Du W, Han Q. Association of pregnancy-associated plasma protein A and vascular endothelial growth factor with pregnancy-induced hypertension. Exp Ther Med 2019;18:1761-7.
3. Smith GCS, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor MJ. 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.
4. Morris RK, Bilagi A, Devani P, Kilby MD. Association of serum PAPP-A levels in first trimester with small for gestational age and adverse pregnancy outcomes: systematic review and meta-analysis. Prenat Diagn 2017;37:253-65.
5. Abdel Moety GAF, Almohamady M, Sherif NA, Raslana AN, Mohamed TF, Abd El Moneam HM, et al. Could first-trimester assessment of placental functions predict preeclampsia and intrauterine growth restriction? A prospective cohort studies. J Matern Fetal Neonat Med 2016;29:413-7.
6. Marttala Ј, Peuhkurinen С, Laitinen P, Gissler M, Nieminen P, Ryynanem M. Low maternal PAPP-A is associated with small-for gestational age newborns and stillbirths. Acta Obstet gynecol Scand 2010;89:1226–8.
7. Saxena AR, Seely EW, Rich-Edwards JW, Wilkins-Haug LE, Karumanchi SA, McElrath TF. First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia. BMC Pregnancy Childbirth 2013;4:13:85.
8. Proctor LK, Toal M, Keating S. Placental size and the prediction of severe early onset intra uterine growth restriction in women with low pregnancy associated plasma protein A. Ultrasounds Obstet Gynecol 2009;34:274-82.
9. Livrinova V, Petrov I, Samardziski I, Jovanovska V, Simeonova-Krstevska S, Todorovska I, et al. Obstetric outcome in pregnant patients with low level of pregnancy-associated plasma protein A in first trimester. Macedonian J Med Sci 2018;6:1028-31.
10. Bilagi A, Burke DL, Riley RD, Mills I, Kilby MD, Katie Morris R. 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;37:705-11.
11. Fillipi E, Stanghton J, Peregrine E, Jones P, Huttly W, Peebles DM. Uterine artery doppler and adverse pregnancy outcome in women with extreme levels of fetoplacental proteins used for down syndrome screening. Ultrasound Obstet Gynecol 2011;37:520-7.
12. Canick JA, Lambert-Messerlian GM, Palomaki GE, Neveux LM, Malone FD, Ball RH, et al. First and second trimester evaluation of risk (FASTER) trial research consortium. Obstet Gynecol 2006;108:1192.
13. Cnossen JS, Morris RK, ter Riet G, Mol BW, van der Post JA, Coomarasamy A, et al. Use of uterine artery Doppler ultrasonography to predict preeclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. CMAJ 2008;178:701-11.
14. Hynhh L, Kingdom J, Akhtar S. Low pregnancy–associated plasma protein A level in the first trimester. Can Fam Physician 2014;60:899–903.
15. Nawathe AR, Christian M, Kim SH, Johnson M, Savvidou MD, Terzidou V. Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. Clin Epigenetics 2016;8:11.
16. Shand MF, Gimovsky A, Macri C. Low PAPP-A levels and pregnancy outcomes. Obstet Gynecol 2018;131:114S.
17. Cowans NJ, Spencer K. First trimester ADAM-12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin like growth factor system. Prenat Diagn 2007;27:264-71.
18. American College of Obstetricians and Gynecologists. Obstetric Care Consensus No. 8: Interpregnancy Care. Obstet Gynecol 2019;133:e51-e72.
19. Jafari RM, Masihi S, Barati M, Maraghi E, Sheibani S, Sheikhvatan M. Value of pregnancy-associated plasma protein-A for predicting adverse pregnancy outcome. Arch Iran Med 2019;22:584-7.
20. Kaijomaa M, Rahkonen L, Ulande VM, Hämäläinen E, Alfthan H, Markkanen H, et al. Low maternal pregnancy-associated plasma protein A during the first trimester of pregnancy and pregnancy outcomes. Int J Gynecol Obstet 2017;136:76-82
21. Odibo AO, Patel KR, Spitalnik A, Odibo L, Huettner P. Placental pathology, first-trimester biomarkers and adverse pregnancy outcomes. J Perinatol 2014;34:186-91.
22. Patil M, Panchanadikar TM, 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.
23. Gupta S, Goyal M, Verma D, Sharma A, Bharadwaj N, Kabra M. Adverse pregnancy outcome in patients with low pregnancy-associated plasma protein-A: The Indian Experience. J. Obstet Gynaecol Res 2015;41:1003-08.
24. Tayyar AT, Tayyar A, Atakul T, Yayla CA, Kilicci C, Eser A, et al. Could first- and second-trimester biochemical markers for Down syndrome have a role in predicting intrahepatic cholestasis of pregnancy?. Arch Med Sci 2018;14:846-50.
25. Aksan Desteli G, Sahin-Uysal N, Cok T, Gulumser C, Kalayci H, Yanik FF. First trimester maternal serum PAPP-A levels and associated pregnancy complications in intrahepatic cholestasis of pregnancy. Clin Exp Obstet Gynecol 2016;43:673-7.
26. Hançerlioğullari N, Aktulay A, Engin-Üstün Y, Ozkan MŞ, Oksuzoglu A, Danişman N. Pregnancy-associated plasma protein A levels are decreased in obstetric cholestasis. Clin Exp Obstet Gynecol 2015;42:617-8.
27. Policy and guidelines: Management of women with a low PAPP-A and normal chromosomes. South Australian Perinatal Practice Guidelines. 2016 available online on https://www.sahealth.sa.gov.au/wps/wcm/connect/067b598044c1bda7, assessed online on 24 May 2020.