First trimester prenatal screening in multiple pregnancies. Part I: comparative analysis of serum proteins PAPP-A and p-hCG in pregnancies conceived spontaneously or by in vitro fertilization

Introduction. Serum proteins PAPP-A (pregnancy-associated plasma protein-A) and β-hCG (the в-subunit of human chorionic gonadotropin) levels are components of the 1st trimester combined screening aimed to detect fetal aneuploidies. In contrast to singleton pregnancies, where the values are well established, this is not the case in twins.

Aim: a comparative analysis of serum proteins PAPP-A and β-hCG levels, as well as parameters PAPP-A MoM and β-hCG MoM in the first trimester during pregnancy with dichorionic diamniotic twins that occurred spontaneously or as a result of in vitro fertilization (IVF).

Materials and methods. The study group included multiple pregnancies as a result of IVF procedure (n = 100) and spontaneous multiple pregnancies (n = 121) considered as controls. The levels of PAPP-A, β-hCG, PAPP-A MoM and β-hCG MoM were compared using nonparametric Mann-Whitney U test.

Results. The PAPP-A MoM level resulted higher in the group of IVF twins (p = 0,007) compared to spontaneous twins: 1.28 [0.97; 1.89] vs. 1.12 [0.87; 1.40] (median [interquartile range]). There were no statistically significant differences in в-hCG levels between the groups of IVF twins and spontaneous twins.

Conclusion. The results justify the need for further study of PAPP-A and β-hCG to establish their association with adverse outcomes in both groups of multiple pregnancies.

1. Brizot M.L., Carvalho M.H., Liao A.W. et al. First-trimester screening for chromosomal abnormalities by fetal nuchal translucency in a Brazilian population. Ultrasound Obstet Gynecol. 2001;18(6):652-5. DOI: 10.1046/j.0960-7692.2001.00588.x.

2. Richardson W.S., Wilson M.C., Nishikawa J., Hayward R.S. The well-built clinical question: a key to evidence-based decisions. ACP J Club. 1995;123(3):A12-3.

3. Cuckle H. Time for total shift to first-trimester screening for Down’s syndrome. Lancet. 2001;358(9294):1658-9. DOI: 10.1016/S0140-6736(01)06724-1.

4. Markelova A.N., Muradyan M.M., Pavlenko K.I. Possibility of using biochemical screening parameters to diagnose pregnancy complications. [Ocenka vozmozhnosti ispol’zovaniya pokazatelej biohimicheskogo skrininga s cel’yu diagnostiki oslozhnenij beremennosti]. VII Mezhdunarodnaya nauchnaya konferenciya «Aktual’nye problemy medicinskoj nauki i obrazovaniya (APMNO-2019)»: sbornik statej. Penza: Izd-vo PGU, 2019. 309-13. (In Russ.). Available at: https://i_med.pnzgu.ru/files/i_med.pnzgu.ru/sbornik_19_ apmno.pdf. (Accessed: 25.01.2020).

5. Morssink L.P., Kornman L.H., Hallahan T.W. 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. DOI: 10.1002/(sici)1097-0223(199802)18:2<147::aid-pd231>3.0.co;2-w.

6. Bersinger N.A., Keller P.J., Naiem A. et al. Pregnancy-specific and pregnancy-associated proteins in threatened abortion. Gynecol Endocrinol. 1987;1(4):379-84. DOI: 10.3109/09513598709082711.

7. Poulsen H.K., Westergaard J.G., Teisner B. et al. Measurements of hCG and PAPP-A in uncommon types of ectopic gestation. Eur J Obstet Gynecol Reprod Biol. 1987;26(1):33-7. DOI: 10.1016/0028-2243(87)90007-4.

8. Khalil A., Rodgers M., Baschat A. et al. ISUOG Practice Guidelines: role of ultrasound in twin pregnancy. [Prakticheskie rekomendacii ISUOG: rol’ ul’trazvukovogo issledovaniya pri vedenii beremennosti dvojnej]. Uttrazvuko-vaya i funkcionatnaya diagnostika. 2017;(2):70-103. (In Russ.).

9. Khalil A., Rodgers M., Baschat A. et al. ISUOG Practice Guidelines: role of ultrasound in twin pregnancy. Ultrasound Obstet Gynecol. 2016;47(2):247—63. DOI: 10.1002/uog.15821.

10. Tul N., Novak-Antolic Z. Serum PAPP-A levels at 10-14 weeks of gestation are altered in women after assisted conception. Prenat Diagn. 2006;26(13):1206-11. DOI: 10.1002/pd.1589.

11. Spencer K., Berry E., Crossley J.A. et al. Is maternal serum total hCG a marker of trisomy 21 in the first trimester of pregnancy? Prenat Diagn. 2000;20(4):311-7. DOI: 10.1002/(sici)1097-0223(200004)20:4<311::aid-pd809>3.0.co;2-p.

12. Linskens I.H., Spreeuwenberg M.D., Blankenstein M.A., van Vugt J.M. Early first-trimester free beta-hCG and PAPP-A serum distributions in monochorionic and dichorionic twins. Prenat Diagn. 2009;29(1):74-8. DOI: 10.1002/pd.2184.

13. Giorgetti C., Vanden Meerschaut F., De Roo C. 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(10):2636-42. DOI: 10.1093/humrep/det295.

14. Gjerris A.C., Tabor A., Loft A. et al. First trimester prenatal screening among women pregnant after IVF/ICSI. Hum Reprod Update. 2012;18(4):350-9. DOI: 10.1093/humupd/dms010.

15. Wald N.J., Rodeck C., Hackshaw A.K. et al. First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen. 2003;10(2):56-104. DOI: 10.1258/096914103321824133.