Hidden signals in placental biochemistry: PAPP-A MoM as an early indicator of Trisomy 21
DOI:
https://doi.org/10.2478/AMB-2026-0057Keywords:
Trisomy 21, PAPP-A, first-trimester screening, maternal age, nuchal translucencyAbstract
Abstract. Purpose: Trisomy 21, or Down Syndrome, is one of the most common chromosomal abnormalities in newborns, appearing in approximately 1 in 700 births, with risk increasing with maternal age. It is a condition of particular importance during first trimester screening. Materials and Methods: We conducted a retrospective cohort study of 2,849 pregnant women at 11+0 and 13+6 weeks of gestation to assess the indicative values of Pregnancy-associated plasma protein-A (PAPP-A) expressed as multiples of the median (MoM), as well as the influence of maternal factors. Differences within groups were made using t-tests or Mann-Whitney U tests for continuous variables, with p < 0.05 considered statistically significant. Results: Out of the 2,849 pregnant women examined, 293 were classified as high-risk pregnancies (risk for screening in the first trimester ≥ 1:250). We confirmed that PAPP-A MoM values were significantly lower in high-risk pregnancies (median 0.68, IQR 0.4-1.1) compared with the low-risk group (median 1.81, IQR 1.2-2.5; p < 0.0001). Nuchal translucency MoM was slightly lower in high-risk pregnancies (0.87, IQR 0.43-1.20) compared with the low-risk group (0.98, IQR 0.86-1.10; p = 0.0394), while CRL did not differ significantly between groups (70.3 mm vs. 63.1 mm; p = 0.4037). Conclusions: These findings support the use of combined screening with maternal demographics, ultrasound, and biochemical markers for accurate first-trimester risk assessment. Further studies suggest adjusting MoM values for maternal characteristics to enhance screening performance, reduce false positives, and enable individualized counseling. Early identification is crucial in high-risk pregnancies to facilitate informed decision-making, targeted check-ups, and reinforce the role of integrated, personalized prenatal screening for optimizing maternal and fetal outcomes.
References
Mazer Zumaeta A, Wright A, Syngelaki A, et al. Screening for trisomies at 11–13 weeks’ gestation: use of PAPP-A, PlGF or both. Prenat Diagn. 2020;40(11):1421-9.
Kagan KO, Wright D, Spencer K et al. First-trimester screening for trisomy 21 by free β-hCG and PAPP-A: impact of maternal and pregnancy characteristics. Ultrasound Obstet Gynecol. 2008;31(5):493-502. doi:10.1002/uog.5332
Zhang Y, Li H, Wang Q et al. Chinese cohort evaluation of PAPP-A ≤0.5 MoM and β-hCG ≥2.75 MoM in trisomy 21 detection. BMC Pregnancy Childbirth. 2023;23:363.
Wang J, Li X, Chen Y et al. Multimarker approach (PAPP-A, free β-hCG, PlGF, AFP + NT) detection rates in 13,000 women. Prenat Diagn. 2023;43(4):473-80.
Ranganathan A, Fresen J, Sarkar P. Association of low first-trimester pregnancy-associated plasma protein A with adverse pregnancy outcomes: an observational study. Obstet Gynecol Rep. 2016;1(1):1-6. doi:10.15761/OGR.1000116
Gonzalez-Gonzalez NL, Gonzalez Davila E, Castro A et al. Effect of pregestational diabetes mellitus on first-trimester placental characteristics: three-dimensional placental volume and power Doppler indices. Placenta. 2014;35(3):147-51. doi:10.1016/j.placenta.2014.01.002
Guibourdenche J, Leguy MC, Pidoux G et al. Biochemical screening for fetal trisomy 21: pathophysiology of maternal serum markers and involvement of the placenta. Int J Mol Sci. 2023;24(8):7669. doi:10.3390/ijms24087669
Kirovakov Z, Hinkova N, Konova E. The impact of inherited thrombophilia on first trimester combined aneuploidy screening parameters. Acta Medica Bulgarica. 2024;51(4):22-27. doi:10.2478/AMB-2024-0073.
Jensen TK, Andersen AN, Bjerregaard B et al. Maternal age and the risk of fetal aneuploidy: a nationwide cohort study in Denmark. Acta Obstet Gynecol Scand. 2023. doi:10.1111/aogs.14713
Hristova I, Naseva E, Yunakova M. Fetal growth abnormalities in overweight and obese pregnant women: a study among Bulgarian pregnant women. Acta Medica Bulgarica. 2026;53(Suppl 1):6-14. doi:10.2478/AMB-2026-0001.
Aiken CE, Smith GC, Best C. Assisted reproductive technology and the risk of birth defects: a systematic review and meta-analysis. JAMA Pediatr. 2016;170(9):890-7. doi:10.1001/jamapediatrics.2016.1011
Tannir G, Boulet S, Jamieson DJ. Genetic risks and outcomes in assisted reproductive technologies. Fertil Steril. 2021;115(5):1101-9. doi:10.1016/j.fertnstert.2021.01.017
Ornoy A. Prenatal origin of obesity and diabetes: an update. Reprod Toxicol. 2015;56:98-106. doi:10.1016/j.reprotox.2015.05.002
Robinson DO, Hall B, Jacobs PA. Parental origin of extra chromosomes in trisomy 21 and its relationship to maternal age. Hum Genet. 2009;126(2):231-7. doi:10.1007/s00439-009-0703-0
Khoshnood B, Loane M, de Vigan C, Dolk H. Long-term trends in prevalence of Down syndrome in Europe. Prenat Diagn. 2011;31(5):487-94. doi:10.1002/pd.2725
Zhu X, Li H, Wang J et al. Association of nuchal translucency with chromosomal abnormalities in a large Chinese cohort. JAMA Netw Open. 2023;6(3):e231234. doi:10.1001/jamanetworkopen.2023.1234
Antonova I, Ivanov D, Yaneva G, et al. Body mass index as a factor influencing oocyte competence and implantation potential – distribution and results in 4,882 women undergoing fertility treatment. Acta Medica Bulgarica. 2024;51(2):8-13. doi:10.2478/AMB-2024-0024.
Souka AP, Snijders RJ, Novakov A et al. Deficient growth in fetuses with trisomy 21 at 11–13+6 weeks of gestation. Ultrasound Obstet Gynecol. 2002;19(2):117-20. doi:10.1002/pd.643
Liao AW, Snijders RJ, Geerts L et al. Fetal growth in chromosomally abnormal fetuses. Ultrasound Obstet Gynecol. 2000;15(1):9-13. doi:10.1046/j.1469-0705.2000.00002.x
Spencer K, Spencer CE, Power M et al. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: three years’ prospective experience. BJOG. 2003;110(3):281-6. doi:10.1046/j.1471-0528.2003.02292.x
Krantz DA, Hallahan TW, Orlandi F et al. First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Obstet Gynecol. 2000;96(2):207-13. doi:10.1016/S0029-7844(00)00895-1
Downloads
Published
Issue
Section
License
Copyright (c) 2026 B. Ilkovska, B. K. Trifunova, F. Ilkovski, D. Gramatkovski, M. Avramovska, P. Avramovski, L. Todorovska (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
You are free to share, copy and redistribute the material in any medium or format under these terms.
Journal Acta Medica Bulgarica 
