Obstet Gynecol Sci.  2020 Apr;63(3):225-230. 10.5468/ogs.2020.63.3.225.

The evaluating of pregnancy-associated plasma protein-A with the likelihood of small for gestational age

• Hoseini MS
• Sheibani S
• Sheikhvatan M

• KMID: 2500411
• DOI: http://doi.org/10.5468/ogs.2020.63.3.225

Abstract

Objective
Recently, strong evidences were obtained on the association between low pregnancy-associated plasma protein-A (PAPP-A) levels in the first trimester and poor outcomes of pregnancy.
Methods
This cross-sectional study was conducted on all pregnant women who were referred to the Obstetrics and Gynecology Clinic at Imam Hossein Hospital in Tehran, Iran in 2014. Women were asked to attend clinical examinations and screening at 11–14 weeks of gestation.
Results
Based on the definition, 14.5% of neonates found to be small for gestational age (SGA). There was a strong association between PAPP-A levels and birth weight. The mean PAPP-A level in the mothers of neonates who were SGA was significantly lower than those without this poor outcome. Based on the receiver operating characteristic curve analysis, serum PAPP-A level was a main determinant in the prediction of SGA neonates.
Conclusion
The serum PAPP-A level at 11–13 weeks of gestation can effectively predict the increased risk for fetal growth retardation. In patients in this study, the best cutoff value for PAPP-A was 0.75 MOM, which signifies that lower levels of this marker can predict fetal growth restriction with high sensitivity and specificity.

Keyword

Pregnancy; Plasma protein-A; Gestational age

Figure

• 

  Fig. 1 The association between pregnancy-associated plasma protein-A (PAPP-A) level and birth weight (BW).

• 

  Fig. 2 The receiver operating characteristic (ROC) curve analysis to determine the value of pregnancy-associated plasma protein-A (PAPP-A) to predict small for gestational age (SGA).

Reference

1. Kagan KO, Wright D, Valencia C, Maiz N, Nicolaides KH. Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A. Hum Reprod. 2008; 23:1968–1975. PMID: 18544579.

2. Kagan KO, Wright D, Spencer K, Molina FS, Nicolaides KH. First-trimester screening for trisomy 21 by free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A: impact of maternal and pregnancy characteristics. Ultrasound Obstet Gynecol. 2008; 31:493–502. PMID: 18432600.

3. 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; 107:1265–1270. PMID: 11028579.

4. 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; 22:778–782. PMID: 12224070.

5. 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; 87:1762–1767. PMID: 11932314.

6. 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; 191:1446–1451. PMID: 15507981.

7. Spencer K, Yu CK, Cowans NJ, Otigbah C, Nicolaides KH. Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free β-hCG and with second-trimester uterine artery Doppler. Prenat Diagn. 2005; 25:949–953. PMID: 16086443.

8. Pilalis A, Souka AP, Antsaklis P, Daskalakis G, Papantoniou N, Mesogitis S, et al. Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler and PAPP-A at 11–14 weeks' gestation. Ultrasound Obstet Gynecol. 2007; 29:135–140. PMID: 17221926.

9. Spencer K, Cowans NJ, Chefetz I, Tal J, Meiri H. First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol. 2007; 29:128–134. PMID: 17149788.

10. Plasencia W, Maiz N, Bonino S, Kaihura C, Nicolaides KH. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2007; 30:742–749. PMID: 17899573.

11. von Dadelszen P, Magee LA, Roberts JM. Subclassification of preeclampsia. Hypertens Pregnancy. 2003; 22:143–148. PMID: 12908998.

12. Witlin GA, Saade GR, Mattar FM, Sibai BM. Predictors of neonatal outcome in women with severe pre-eclampsia or eclampsia between 24 and 33 weeks' gestation. Am J Obstet Gynecol. 1999; 1:S19.

13. Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ. 2001; 323:1213–1217. PMID: 11719411.

14. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation. Lancet. 1998; 352:343–346. PMID: 9717920.

15. Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience. BJOG. 2003; 110:281–286. PMID: 12628268.

16. Nicolaides KH, Spencer K, Avgidou K, Faiola S, Falcon O. Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening. Ultrasound Obstet Gynecol. 2005; 25:221–226. PMID: 15736186.

17. Ciobanu A, Rouvali A, Syngelaki A, Akolekar R, Nicolaides KH. Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35–37 weeks' gestation. Am J Obstet Gynecol. 2019; 220:486.e1–486.11. PMID: 30707967.

18. McCowan LM, Thompson JM, Taylor RS, Baker PN, North RA, Poston L, et al. Prediction of small for gestational age infants in healthy nulliparous women using clinical and ultrasound risk factors combined with early pregnancy biomarkers. PLoS One. 2017; 12:e0169311. PMID: 28068394.

19. Agarwal R, Kumari R, Mehndiratta M, Radhakrishnan G, Faridi MM, Chandra N. Pregnancy-associated plasma protein A levels in late first trimester pregnancies with small-for-gestational age neonates: a prospective case-control study. J Obstet Gynaecol India. 2017; 67:247–252. PMID: 28706362.

20. Sung KU, Roh JA, Eoh KJ, Kim EH. Maternal serum placental growth factor and pregnancy-associated plasma protein A measured in the first trimester as parameters of subsequent pre-eclampsia and small-for-gestational-age infants: a prospective observational study. Obstet Gynecol Sci. 2017; 60:154–162. PMID: 28344956.

21. Hansen YB, Myrhøj V, Jørgensen FS, Oxvig C, Sørensen S. First trimester PAPP-A2, PAPP-A and hCGβ in small-for-gestational-age pregnancies. Clin Chem Lab Med. 2016; 54:117–123. PMID: 26544105.

22. D'Antonio F, Rijo C, Thilaganathan C, Akolekar B, Khalil R, Papageourgiou A, et al. Association between first-trimester maternal serum pregnancy-associated plasma protein-A and obstetric complications. Prenat Diagn. 2013; 33:839–847. PMID: 23613261.

23. Loncar D, Varjacić 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; 70:46–50. PMID: 23401929.

24. Kirkegaard I, Henriksen TB, Uldbjerg N. Early fetal growth, PAPP-A and free β-hCG in relation to risk of delivering a small-for-gestational age infant. Ultrasound Obstet Gynecol. 2011; 37:341–347. PMID: 20737455.

25. Salvig JD, Kirkegaard I, Winding TN, Henriksen TB, Tørring N, Uldbjerg N. Low PAPP-A in the first trimester is associated with reduced fetal growth rate prior to gestational week 20. Prenat Diagn. 2010; 30:503–508. PMID: 20509148.

26. 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; 29:1244–1248. PMID: 19862778.

27. 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; 32:724–729. PMID: 22553082.