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Prediction of Adverse Obstetric Outcomes by First Trimester Screening with Free β-hCG and PAPP-A: A Prospective Study of 889 Singleton Pregnancies

Year 2020, Volume: 17 Issue: 4, 497 - 503, 31.12.2020
https://doi.org/10.38136/jgon.760133

Abstract

Aim: We aimed to analyze the association of first-trimester screening biomarkers (PAPP-A and free β-hCG) that correspond specific percentile with adverse pregnancy outcomes, including preterm labor, preterm delivery, gestational diabetes mellitus (GDM), gestational hypertension, preeclampsia, low birth weight (LBW), small for gestational age (SGA), large for gestational age (LGA), intrauterine growth restriction (IUGR), macrosomia, and intrauterine exitus (IUEX).

Materials and Method: This prospective study conducted between 1st May 2011 and 1st May 2012 at Gazi University Faculty of Medicine, Turkey. We recruited only singleton pregnancies. The first-trimester screening test was performed between 11-14 weeks of gestation.

Results: Eight hundred eighty-nine of them met the inclusion criteria for our study. The median age was 29 (26-33) years. Median free β-hCG MoM and PAPP-A MoM were 1.0 (0.7 - 1.48) and 1.04 (0.73 - 1.46), respectively. The most common adverse obstetric outcomes were preterm labor 164 (18.4%), threatened abortion 95 (10.7%), and GDM 75 (8.4%). There was a linear trend with PAPP-A MoM and SGA, LBW, preterm delivery (p=<0.0000001, 0.033, and 0.03, respectively). When PAPP-A MoM results were categorized under three groups as ≤0.42 (5th percentile), >2.5 (95th percentile), and 0.73-1.47 (25th -75th), a significant difference between there groups were detected for SGA (<0.0000001), LBW (0.01), IUEX (0.00005), preterm labor (0.002), IUGR (0.006). Only preterm labor showed a significant linear trend for β-hCG MoM values (p =0.007). However, this significance was not detected when β-hCG MoM values were categorized as ≤0.40 (5th percentile), >2.9 (95th percentile), and 0.75-1.49 (25th -75th) (p=0.47). The correlation coefficient of birth weight and PAPP-A MoM was 0.133, which is negligible (p=0.0001).

Conclusion: Our study suggested the possibility of predicting the women with the risk of adverse obstetric outcomes by using first-trimester screening biomarkers, namely maternal free β-hCG, and PAPP-A levels.

Supporting Institution

Yok

Thanks

Authors would like to thank to the patients participated in the study.

References

  • 1. Kane SC, Costa Fda S, Brennecke S. First trimester biomarkers in the prediction of later pregnancy complications. Biomed Res Int. 2014;2014:807196.
  • 2. Pihl K, Sorensen TL, Norgaard-Pedersen B, Larsen SO, Nguyen TH, Krebs L, et al. First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre-term delivery in a cohort of non-selected women. Prenat Diagn. 2008;28(3):247-53.
  • 3. 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.
  • 4. 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(13):1244-8.
  • 5. Salvig JD, Kirkegaard I, Winding TN, Henriksen TB, Torring 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(6):503-8.
  • 6. Canini S, Prefumo F, Pastorino D, Crocetti L, Afflitto CG, Venturini PL, et al. Association between birth weight and first-trimester free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. Fertil Steril. 2008;89(1):174-8.
  • 7. Ranta JK, Raatikainen K, Romppanen J, Pulkki K, Heinonen S. Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption. Eur J Obstet Gynecol Reprod Biol. 2011;157(1):48-52.
  • 8. Savvidou MD, Syngelaki A, Muhaisen M, Emelyanenko E, Nicolaides KH. First trimester maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus. BJOG. 2012;119(4):410-6.
  • 9. Costa MA. The endocrine function of human placenta: an overview. Reproductive biomedicine online. 2016;32(1):14-43.
  • 10. Bowman CJ, Streck RD, Chapin RE. Maternal-placental insulin-like growth factor (IGF) signaling and its importance to normal embryo-fetal development. Birth Defects Res B Dev Reprod Toxicol. 2010;89(4):339-49.
  • 11. Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proceedings of the National Academy of Sciences. 1999;96(6):3149-53.
  • 12. Conover CA, Bale LK, Overgaard MT, Johnstone EW, Laursen UH, Füchtbauer E-M, et al. Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. Development. 2004;131(5):1187-94.
  • 13. Stenman UH, Tiitinen A, Alfthan H, Valmu L. The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update. 2006;12(6):769-84.
  • 14. Ong CY, Liao AW, Spencer K, Munim S, Nicolaides KH. First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG. 2000;107(10):1265-70.
  • 15. Sharp AN, Alfirevic Z. First trimester screening can predict adverse pregnancy outcomes. Prenat Diagn. 2014;34(7):660-7.
  • 16. American Diabetes A. Gestational diabetes mellitus. Diabetes Care. 2003;26 Suppl 1:S103-5.
  • 17. Gagnon A, Wilson RD, Society Of O, Gynaecologists Of Canada Genetics C. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008;30(10):918-32.
  • 18. Ghasemi-Tehrani H, Sadeghian A, Entezari R. Relationship Between Pregnancy Complications and Serum Pregnancy Associated-Plasma-Protein-A and Free-beta-Human Chorionic Gonadotropin in the First Trimester Among Iranian Women. J Family Reprod Health. 2017;11(4):219-24.
  • 19. Arai S, Arai C, Fujimaki M, Iwamoto Y, Kawarada M, Saito Y, et al. Cutaneous tumour-like lesions due to poxvirus infection in Chilean flamingos. J Comp Pathol. 1991;104(4):439-41.
  • 20. 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(12):990-6.
  • 21. Cowans NJ, Spencer K. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system. Prenat Diagn. 2007;27(3):264-71.
  • 22. Morssink LP, Kornman LH, Hallahan TW, Kloosterman MD, Beekhuis JR, de 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.
  • 23. Tarim E, HACIVELİOĞLU SÖ, Cok T, BAĞIŞ HT. First trimester maternal serum PAPP-A levels and macrosomia in nondiabetic mothers. Turkish Journal of Medical Sciences. 2011;41(4):581-6.
  • 24. Wells G, Bleicher K, Han X, McShane M, Chan YF, Bartlett A, et al. Maternal Diabetes, Large-for-Gestational-Age Births, and First Trimester Pregnancy-Associated Plasma Protein-A. J Clin Endocrinol Metab. 2015;100(6):2372-9.
  • 25. Peterson SE, Simhan HN. First-trimester pregnancy-associated plasma protein A and subsequent abnormalities of fetal growth. Am J Obstet Gynecol. 2008;198(5):e43-5.
  • 26. Cignini P, Maggio Savasta L, Gulino FA, Vitale SG, Mangiafico L, Mesoraca A, et al. Predictive value of pregnancy-associated plasma protein-A (PAPP-A) and free beta-hCG on fetal growth restriction: results of a prospective study. Arch Gynecol Obstet. 2016;293(6):1227-33.
  • 27. 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(2):116-9.
  • 28. 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. Taiwan J Obstet Gynecol. 2016;55(1):72-5.
  • 29. Goetzinger KR, Cahill AG, Macones GA, Odibo AO. Association of first-trimester low PAPP-A levels with preterm birth. Prenat Diagn. 2010;30(4):309-13.
  • 30. Livrinova V, Petrov I, Samardziski I, Jovanovska V, Boshku AA, Todorovska I, et al. Clinical Importance of Low Level of PAPP-A in First Trimester of Pregnancy - An Obstetrical Dilemma in Chromosomally Normal Fetus. Open Access Maced J Med Sci. 2019;7(9):1475-9.
  • 31. 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(4):1446-51.
  • 32. 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(4):1762-7.
  • 33. Bersinger NA, Smarason AK, Muttukrishna S, Groome NP, Redman CW. Women with preeclampsia have increased serum levels of pregnancy-associated plasma protein A (PAPP-A), inhibin A, activin A and soluble E-selectin. Hypertens Pregnancy. 2003;22(1):45-55.
  • 34. 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. Experimental and therapeutic medicine. 2019;18(3):1761-7.
  • 35. Karahasanovic A, Sorensen S, Nilas L. First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia. Clin Chem Lab Med. 2014;52(4):521-5.
  • 36. 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.
  • 37. 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(3):253-65.
  • 38. Ramezani S, Ahmadi Doulabi M, 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. Journal of Reproduction & Infertility. 2020;21(2):130-7.
  • 39. Donovan BM, Nidey NL, Jasper EA, Robinson JG, Bao W, Saftlas AF, et al. First trimester prenatal screening biomarkers and gestational diabetes mellitus: A systematic review and meta-analysis. PLoS One. 2018;13(7):e0201319.
  • 40. Spencer K, Cowans NJ. The association between gestational diabetes mellitus and first trimester aneuploidy screening markers. Ann Clin Biochem. 2013;50(Pt 6):603-10.
  • 41. Ozdamar O, Gun I, Keskin U, Kocak N, Mungen E. The role of maternal serumbeta-HCG and PAPP-A levels at gestational weeks 10 to 14 in the prediction of pre-eclampsia. Pak J Med Sci. 2014;30(3):568-73.
  • 42. Yliniemi A, Makikallio K, Korpimaki T, Kouru H, Marttala J, Ryynanen M. Combination of PAPPA, fhCGbeta, AFP, PlGF, sTNFR1, and Maternal Characteristics in Prediction of Early-onset Preeclampsia. Clin Med Insights Reprod Health. 2015;9:13-20.
  • 43. Pakniat H, Bahman A, Ansari I. The Relationship of Pregnancy-Associated Plasma Protein A and Human Chorionic Gonadotropin with Adverse Pregnancy Outcomes: A Prospective Study. J Obstet Gynaecol India. 2019;69(5):412-9.

Birinci Trimester Taramasında Bakılan Serum Belirteçlerinden β-hCG ve PAPP-A’nın Kötü Obstetrik Sonuçları Öngörmede Etkisi: 889 Tekil Gebelik ile yapılan Prospektif Bir Çalışma

Year 2020, Volume: 17 Issue: 4, 497 - 503, 31.12.2020
https://doi.org/10.38136/jgon.760133

Abstract

Amaç: Bu çalışmada birinci trimester tarama testinde değerlendirilen serum belirteçlerinden PAPP-A ve serbest β-hCG nin preterm eylem, preterm doğum, gestasyonel diyabetes mellitus (GDM), gebelik hipertansiyonu, preeklampsi, düşük doğum ağırlığı (DDA), gebelik yaşına göre küçük (SGA), gebelik yaşına göre büyük (LGA), intrauterin gelişme geriliği (IUGR), makrozomi, intrauterin eksitus (IUEX) gibi gebelik komplikasyonları ile ilişkisini değerlendirmeyi amaçladık.

Gereçler ve Yöntem: Bu prospektif çalışma 1 Mayıs 2011 ile 1 Mayıs 2012 arasında Gazi Üniversitesi Tıp Fakültesi Hastanesi’nde yürütülmüştür. Tekil gebelik nedeni ile takip edilen ve 11-14. haftalarda birinci trimester tarama testi yapılmış 889 kadın çalışmaya dahil edilmiştir.

Bulgular: Çalışmaya kriterlere uygun olan 889 kadın dahil edildi. Yaş ortanca değeri 29 (26-33) olup serbest β-hCG MoM ve PAPP-A MoM ortanca değerleri sırasıyla 1.0 (0.7- 1.48) ve 1.04 (0.73- 1.46) idi. En sık gözlenen gebelik komplikasyonları preterm eylem 164 (18.4%), düşük tehdidi 95 (10.7%), ve GDM 75 (8.4%) idi. PAPP-A MoM ile SGA, DDA ve preterm doğum arasında doğrusal bir ilişki izlendi (sırasıyla, p=<0.0000001, 0.033, ve 0.03). PAPP-A MoM değerleri ≤0.42 (5. persentil),>2.5 (95. persentil), ve 0.73-1.47 (25.-75. persentil) olmak üzere üç kategoriye ayrıldığında bu üç grup arasında SGA (<0.0000001), DDA (0.01), IUEX (0.00005), preterm eylem (0.002), ve IUGR (0.006) için anlamlı farklılık izlendi. Sadece preterm eylem ile serbest β-hCG MoM değerleri arasında doğrusal bir ilişki izlendi (p =0.007). Ancak bu ilişki β-hCG MoM değerleri ≤0.40 (5. persentil), >2.9 (95. persentil), ve 0.75-1.49 (25.-75. persentil) olmak üzere üç grupta kategorize edildiğinde kayboldu (p=0.47). Doğum ağırlığı ve PAPP-A MoM değerleri arasında göz ardı edilebilir düzeyde düşük bir korelasyon izlendi (r=0.133, p=0.0001).

Sonuç: Bu çalışma birinci trimesterde bakılan serum biyokimyasal belirteçlerinden serbest β-hCG ve PAPP-A değerlerinin bazı olumsuz gebelik komplikasyonlarını öngörmede faydalı olabileceğini göstermektedir.

References

  • 1. Kane SC, Costa Fda S, Brennecke S. First trimester biomarkers in the prediction of later pregnancy complications. Biomed Res Int. 2014;2014:807196.
  • 2. Pihl K, Sorensen TL, Norgaard-Pedersen B, Larsen SO, Nguyen TH, Krebs L, et al. First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre-term delivery in a cohort of non-selected women. Prenat Diagn. 2008;28(3):247-53.
  • 3. 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.
  • 4. 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(13):1244-8.
  • 5. Salvig JD, Kirkegaard I, Winding TN, Henriksen TB, Torring 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(6):503-8.
  • 6. Canini S, Prefumo F, Pastorino D, Crocetti L, Afflitto CG, Venturini PL, et al. Association between birth weight and first-trimester free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. Fertil Steril. 2008;89(1):174-8.
  • 7. Ranta JK, Raatikainen K, Romppanen J, Pulkki K, Heinonen S. Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption. Eur J Obstet Gynecol Reprod Biol. 2011;157(1):48-52.
  • 8. Savvidou MD, Syngelaki A, Muhaisen M, Emelyanenko E, Nicolaides KH. First trimester maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus. BJOG. 2012;119(4):410-6.
  • 9. Costa MA. The endocrine function of human placenta: an overview. Reproductive biomedicine online. 2016;32(1):14-43.
  • 10. Bowman CJ, Streck RD, Chapin RE. Maternal-placental insulin-like growth factor (IGF) signaling and its importance to normal embryo-fetal development. Birth Defects Res B Dev Reprod Toxicol. 2010;89(4):339-49.
  • 11. Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proceedings of the National Academy of Sciences. 1999;96(6):3149-53.
  • 12. Conover CA, Bale LK, Overgaard MT, Johnstone EW, Laursen UH, Füchtbauer E-M, et al. Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. Development. 2004;131(5):1187-94.
  • 13. Stenman UH, Tiitinen A, Alfthan H, Valmu L. The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update. 2006;12(6):769-84.
  • 14. Ong CY, Liao AW, Spencer K, Munim S, Nicolaides KH. First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG. 2000;107(10):1265-70.
  • 15. Sharp AN, Alfirevic Z. First trimester screening can predict adverse pregnancy outcomes. Prenat Diagn. 2014;34(7):660-7.
  • 16. American Diabetes A. Gestational diabetes mellitus. Diabetes Care. 2003;26 Suppl 1:S103-5.
  • 17. Gagnon A, Wilson RD, Society Of O, Gynaecologists Of Canada Genetics C. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008;30(10):918-32.
  • 18. Ghasemi-Tehrani H, Sadeghian A, Entezari R. Relationship Between Pregnancy Complications and Serum Pregnancy Associated-Plasma-Protein-A and Free-beta-Human Chorionic Gonadotropin in the First Trimester Among Iranian Women. J Family Reprod Health. 2017;11(4):219-24.
  • 19. Arai S, Arai C, Fujimaki M, Iwamoto Y, Kawarada M, Saito Y, et al. Cutaneous tumour-like lesions due to poxvirus infection in Chilean flamingos. J Comp Pathol. 1991;104(4):439-41.
  • 20. 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(12):990-6.
  • 21. Cowans NJ, Spencer K. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system. Prenat Diagn. 2007;27(3):264-71.
  • 22. Morssink LP, Kornman LH, Hallahan TW, Kloosterman MD, Beekhuis JR, de 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.
  • 23. Tarim E, HACIVELİOĞLU SÖ, Cok T, BAĞIŞ HT. First trimester maternal serum PAPP-A levels and macrosomia in nondiabetic mothers. Turkish Journal of Medical Sciences. 2011;41(4):581-6.
  • 24. Wells G, Bleicher K, Han X, McShane M, Chan YF, Bartlett A, et al. Maternal Diabetes, Large-for-Gestational-Age Births, and First Trimester Pregnancy-Associated Plasma Protein-A. J Clin Endocrinol Metab. 2015;100(6):2372-9.
  • 25. Peterson SE, Simhan HN. First-trimester pregnancy-associated plasma protein A and subsequent abnormalities of fetal growth. Am J Obstet Gynecol. 2008;198(5):e43-5.
  • 26. Cignini P, Maggio Savasta L, Gulino FA, Vitale SG, Mangiafico L, Mesoraca A, et al. Predictive value of pregnancy-associated plasma protein-A (PAPP-A) and free beta-hCG on fetal growth restriction: results of a prospective study. Arch Gynecol Obstet. 2016;293(6):1227-33.
  • 27. 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(2):116-9.
  • 28. 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. Taiwan J Obstet Gynecol. 2016;55(1):72-5.
  • 29. Goetzinger KR, Cahill AG, Macones GA, Odibo AO. Association of first-trimester low PAPP-A levels with preterm birth. Prenat Diagn. 2010;30(4):309-13.
  • 30. Livrinova V, Petrov I, Samardziski I, Jovanovska V, Boshku AA, Todorovska I, et al. Clinical Importance of Low Level of PAPP-A in First Trimester of Pregnancy - An Obstetrical Dilemma in Chromosomally Normal Fetus. Open Access Maced J Med Sci. 2019;7(9):1475-9.
  • 31. 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(4):1446-51.
  • 32. 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(4):1762-7.
  • 33. Bersinger NA, Smarason AK, Muttukrishna S, Groome NP, Redman CW. Women with preeclampsia have increased serum levels of pregnancy-associated plasma protein A (PAPP-A), inhibin A, activin A and soluble E-selectin. Hypertens Pregnancy. 2003;22(1):45-55.
  • 34. 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. Experimental and therapeutic medicine. 2019;18(3):1761-7.
  • 35. Karahasanovic A, Sorensen S, Nilas L. First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia. Clin Chem Lab Med. 2014;52(4):521-5.
  • 36. 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.
  • 37. 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(3):253-65.
  • 38. Ramezani S, Ahmadi Doulabi M, 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. Journal of Reproduction & Infertility. 2020;21(2):130-7.
  • 39. Donovan BM, Nidey NL, Jasper EA, Robinson JG, Bao W, Saftlas AF, et al. First trimester prenatal screening biomarkers and gestational diabetes mellitus: A systematic review and meta-analysis. PLoS One. 2018;13(7):e0201319.
  • 40. Spencer K, Cowans NJ. The association between gestational diabetes mellitus and first trimester aneuploidy screening markers. Ann Clin Biochem. 2013;50(Pt 6):603-10.
  • 41. Ozdamar O, Gun I, Keskin U, Kocak N, Mungen E. The role of maternal serumbeta-HCG and PAPP-A levels at gestational weeks 10 to 14 in the prediction of pre-eclampsia. Pak J Med Sci. 2014;30(3):568-73.
  • 42. Yliniemi A, Makikallio K, Korpimaki T, Kouru H, Marttala J, Ryynanen M. Combination of PAPPA, fhCGbeta, AFP, PlGF, sTNFR1, and Maternal Characteristics in Prediction of Early-onset Preeclampsia. Clin Med Insights Reprod Health. 2015;9:13-20.
  • 43. Pakniat H, Bahman A, Ansari I. The Relationship of Pregnancy-Associated Plasma Protein A and Human Chorionic Gonadotropin with Adverse Pregnancy Outcomes: A Prospective Study. J Obstet Gynaecol India. 2019;69(5):412-9.
There are 43 citations in total.

Details

Primary Language English
Subjects Obstetrics and Gynaecology
Journal Section Research Articles
Authors

Şule Yıldız 0000-0002-4803-7043

Ümit Yasemin Sert 0000-0003-0862-4793

Esra Bilir 0000-0003-4499-6543

Engin Türkgeldi This is me 0000-0002-5008-3292

Tuncay Nas This is me 0000-0002-6046-7249

Publication Date December 31, 2020
Submission Date July 9, 2020
Acceptance Date September 11, 2020
Published in Issue Year 2020 Volume: 17 Issue: 4

Cite

Vancouver Yıldız Ş, Sert ÜY, Bilir E, Türkgeldi E, Nas T. Prediction of Adverse Obstetric Outcomes by First Trimester Screening with Free β-hCG and PAPP-A: A Prospective Study of 889 Singleton Pregnancies. JGON. 2020;17(4):497-503.