Farname Inc. in collaboration with Iranian Society of Gynecology Oncology

Authors

1 Reproductive Health Research Center, Department of Obstetrics & Gynecology, Al-zahra Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

2 Reproductive Health Research Center, Department of Obstetrics & Gynecology, Al-Zahra Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

3 School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Abstract

Background and objective:   The initial diagnosis of predictive markers is essential for the IUGR. High levels of PAPP-A lead to increased levels of free IGF-1, which in turn reflects the function of the placenta and the fetus normal growth. The objective of this study was to compare the level of PAPP-A in pregnancy weeks 11-14 in women with and without intrauterine growth restriction and to assess the ability of this marker to predict adverse outcomes in pregnancy.
 
Methods:  In this Comparative Cross-sectional study, 227 pregnant women were studied during 2017. Mothers were divided into two main groups with and without intrauterine growth restriction. The relevant data, including birth weight, preeclampsia, gestational diabetes, Apgar score, and PAPP-A, were recorded on special forms. Data analysis was done using SPSS-21 software.
 
Results: The mean age of participating women in this study was 28.8 ± 5.6 years. The median (IOR) number of gravidity and Gestational weight gain was 1 (1) and 12 (7) kg respectively. The difference in median (IOR) PAPP-A in patients with and without IUGR was statistically significant 0.64(0.57) and 1 (0.57), respectively, P= 0.001.The cut-off point for PAPP-A was 0.73 with a sensitivity=72.2% (95% CI: 64.32-79.16%) and a specify =60.5% (95% CI: 48.65 -71.56%).
 
Conclusion: The results of this study confirm the relationship between low levels of PAPP-A and adverse outcomes of pregnancy. In the present study, the optimal cut-off point (0.73) is higher than other studies, which can be due to racial and epidemiological differences.

Keywords

  1. 1. Cunningham F & Bloom S.L., & Dashe J.S., & Hoffman B.L., & Casey B.M., & Spong C.Y. & LKJ. Williams Obstetrics [Internet]. 25e, editor. McGraw Hill; 2018. Available from: https://accessmedicine.mhmedical.com/content.aspx?bookid=1918&sectionid=138822591 2. Gynecologists AC of O and. ACOG Practice Bulletin No. 204: fetal growth restriction. Obstet Gynecol. 2019;133(2):e97–109. doi: 10.1097/AOG.0000000000003070. PMID: 30681542. 3. Conde‐Agudelo A, Papageorghiou AT, Kennedy SH, Villar J. Novel biomarkers for predicting intrauterine growth restriction: a systematic review and meta‐analysis. BJOG. 2013 May;120(6):681-94. doi: 10.1111/1471-0528.12172. Epub 2013 Feb 11. PMID: 23398929. 4. Leijnse JEW, de Heus R, de Jager W, Rodenburg W, Peeters LLH, Franx A, et al. First trimester placental vascularization and angiogenetic factors are associated with adverse pregnancy outcome. Pregnancy Hypertens. 2018;13:87–94. doi: 10.1016/j.preghy.2018.04.008. Epub 2018 Apr 11. PMID: 30177079. 5. Abdi F, Aghaie Z, Rahnemaei FA, Alimoradi Z. A systematic review of first trimester biochemical and molecular predictive tests for preeclampsia. Curr Hypertens Rev. 2018;14(1):21-28. doi: 10.2174/1573402114666180416160425. PMID: 29658438. 6. Barrios V, Chowen JA, Martín-Rivada Á, Guerra-Cantera S, Pozo J, Yakar S, et al. Pregnancy-associated plasma protein (PAPP)-A2 in physiology and disease. Cells. 2021 Dec 18;10(12):3576. doi: 10.3390/cells10123576. PMID: 34944082; PMCID: PMC8700087. 7. Sferruzzi‐Perri AN, Sandovici I, Constancia M, Fowden AL. Placental phenotype and the insulin‐like growth factors: resource allocation to fetal growth. J Physiol. 2017;595(15):5057–93. doi: 10.1113/JP273330. Epub 2017 May 23. PMID: 28337745; PMCID: PMC5538190. 8. 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. 2016/12/25. 2017;37(3):253–65. doi: 10.1002/pd.5001. Epub 2017 Feb 17. PMID: 28012202. 9. Kaijomaa M, Ulander VM, Hämäläinen E, Alfthan H, Markkanen H, Heinonen S, et al. The risk of adverse pregnancy outcome among pregnancies with extremely low maternal PAPP-A. Prenat Diagn. 2016/10/18. 2016;36(12):1115–20. doi: 10.1002/pd.4946. Epub 2016 Nov 18. PMID: 27750370. 10. Antsaklis P, Fasoulakis Z, Theodora M, Diakosavvas M, Kontomanolis EN. Association of low maternal pregnancy-associated plasma protein a with adverse perinatal outcome. Cureus. 2019;11(6). doi: 10.7759/cureus.4912. PMID: 31423389; PMCID: PMC6692091. 11. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011/01/07. 2011;31(1):7–15. doi: 10.1002/pd.2637. PMID: 21210475. 12. Ong CYT, 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 Oct;107(10):1265-70. doi: 10.1111/j.1471-0528.2000.tb11618.x. PMID: 11028579. 13. Spencer K, Yu CK, Cowans NJ, Otigbah C, Nicolaides KH. Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free beta-hCG and with second-trimester uterine artery Doppler. Prenat Diagn. 2005 Oct;25(10):949-53. doi: 10.1002/pd.1251. PMID: 16086443. 14. Poon LC, Maiz N, Valencia C, Plasencia W, Nicolaides KH. First-trimester maternal serum pregnancy-associated plasma protein-A and pre-eclampsia. Ultrasound Obstet Gynecol. 2009 Jan;33(1):23-33. doi: 10.1002/uog.6280. PMID: 19090499. 15. Goetzinger KR, Singla A, Gerkowicz S, Dicke JM, Gray DL, Odibo AO. The efficiency of first-trimester serum analytes and maternal characteristics in predicting fetal growth disorders. Am J Obstet Gynecol. 2009;201(4):412. e1-412. e6. 16. Grill S, Rusterholz C, Zanetti-Dällenbach R, Tercanli S, Holzgreve W, Hahn S, et al. Potential markers of preeclampsia--a review. Reprod Biol Endocrinol. 2009/07/16. 2009;7:70. doi: 10.1186/1477-7827-7-70. PMID: 19602262; PMCID: PMC2717076. 17. Deveci K, Sogut E, Evliyaoglu O, Duras N. Pregnancy‐associated plasma protein‐A and C‐reactive protein levels in pre‐eclamptic and normotensive pregnant women at third trimester. J Obstet Gynaecol Res. 2009;35(1):94–8. doi: 10.1111/j.1447-0756.2008.00835.x. PMID: 19215554. 18. Kuc S, Wortelboer EJ, van 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. Obs Gynecol Surv. 2011/07/16. 2011;66(4):225–39. doi: 10.1097/OGX.0b013e3182227027. PMID: 21756405. 19. Lean SC, Heazell AEP, Dilworth MR, Mills TA, Jones RL. Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women. Sci Rep. 2017/08/31. 2017;7(1):9677. doi: 10.1038/s41598-017-09814-w. PMID: 28852057; PMCID: PMC5574918. 20. Carolan M, Frankowska D. Advanced maternal age and adverse perinatal outcome: a review of the evidence. Midwifery. 2010/10/05. 2011;27(6):793–801. doi: 10.1016/j.midw.2010.07.006. Epub 2010 Oct 2. PMID: 20888095. 21. Lončar D, Varjačić M, Arsenijević S. Significance of pregnancy-associated plasma protein A (PAPP-A) concentration determination in the assessment of final outcome of pregnancy. Vojnosanit Pregl. 2013;70(1):46–50. doi: 10.2298/vsp110530023l. PMID: 23401929. 22. Albu AR, Anca AF, Horhoianu V V, Horhoianu IA. Predictive factors for intrauterine growth restriction. J Med Life. 2014 Jun 15;7(2):165-71. Epub 2014 Jun 25. PMID: 25408721; PMCID: PMC4197512. 23. Sharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Clin Med Insights Pediatr. 2016/07/22. 2016;10:67–83. doi: 10.4137/CMPed.S40070. PMID: 27441006; PMCID: PMC4946587. 24. Ramezani S, Doulabi MA, Saqhafi H, Alipoor M. Prediction of Gestational Diabetes by Measuring the Levels of Pregnancy Associated Plasma Protein-A (PAPP-A) During Gestation Weeks 11–14. J Reprod Infertil. 2020 Apr-Jun;21(2):130-137. PMID: 32500016; PMCID: PMC7253940. 25. Petry CJ, Ong KK, Hughes IA, Acerini CL, Frystyk J, Dunger DB. Early pregnancy-associated plasma protein A concentrations are associated with third trimester insulin sensitivity. J Clin Endocrinol Metab. 2017 Jun 1;102(6):2000-2008. doi: 10.1210/jc.2017-00272. PMID: 28323969; PMCID: PMC5464396. 26. Ekin A, Gezer C, Taner CE, Özeren M. The association between low PAPP-A levels at first trimester and poor pregnancy outcomes. Perinat J. 2014;22(3):142–6. 27. Gupta S, Goyal M, Verma D, Sharma A, Bharadwaj N, Kabra M, et al. Adverse pregnancy outcome in patients with low pregnancy‐associated plasma protein‐A: The Indian Experience. J Obstet Gynaecol Res. 2015;41(7):1003–8. doi: 10.1111/jog.12662. Epub 2015 Mar 15. PMID: 25773764.