Results of complex prenatal examinations in cases of chromosome 21 imbalance in the fetus


  • I.Yu. Gordienko SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • T.V. Nikitchina SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • O.O. Vashchenko SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • O.M. Tarapurova SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • A.V. Velychko SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • K.V. Rachenko SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • G.O. Grebinichenko SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine



prenatal diagnosis, chromosomal anomalies, karyotype, chromosome 21, trisomy 21, Down Syndrome, deletion 21, confined placental mosaicism, congenital malformations


Purpose - to characterize the cases of chromosome 21 imbalance in fetuses of high-risk pregnant women, to describe prenatal cytogenetic diagnosis and associated ultrasound findings - structural anomalies and soft markers.

Materials and methods. The results of complex prenatal examination of high-risk pregnant women in the Department of Fetal Medicine of the SI “Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine” during 5 years period were analyzed: results of ultrasound and cytogenetic exams of 200 cases of chromosome 21 imbalance in the fetus.

Results. Among 4,748 prenatal cytogenetic testing of fetuses of high-risk women abnormal karyotypes with an imbalance of chromosome 21 were found in 200 (4.21%) cases. In the majority of cases Down's syndrome (DS) was diagnosed (n=199; 99.5%), in 1 (0.2%) case - deletion of chromosome 21. In DS, regular trisomy of chromosome 21 was found in 191 (95.97%) cases, translocant forms - in 5 (2.51%) cases, in 1 (0.5%) case there was there was an additional sex chromosome, and in 1 (0.5%) - a variant with two cell lines. In 1 (0.5%) case limited placental mosaicism was present, with a false negative result that required verification by the analysis of fetal lymphocytes obtained during cordocentesis. Advanced maternal age (≥35 years) was registered in less than half of fetal DS cases (n=92/199, 46.2%). The main indications for invasive procedures and their types are described. It was demonstrated that ultrasound findings (structural anomalies and/or “soft” markers for chromosomal pathology) were present in 78% of fetal chromosome 21 imbalance; nevertheless in 22% ultrasound findings were absent, and the indication for invasive procedures were advanced maternal age or isolated changes of biochemical markers.

Conclusions. Chromosome 21 imbalance in fetuses is mainly represented by trisomy, cases of chromosome 21 deletion are extremely rare. Targeted ultrasound examination is important for screening and diagnosis of fetal chromosomal abnormalities. High-risk pregnant women shouldn’t be reassured in case of “normal” ultrasound exam results. Under certain conditions, it is advisable to perform placental biopsy in the II trimester of pregnancy, but only in specialized tertiary centers or departments.

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.


Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, Bianchi DW et al. (2020). Down syndrome. Nature reviews. Disease primers. 6(1): 9.; PMid:32029743 PMCid:PMC8428796

Baranov VS, Kuznetsova TV. (2007). Citogenetika yembrionalnogo razvitiya cheloveka. SPb: Izdatelstvo N-L: 640.

Biaduń-Popławska A, Jamsheer A, Henkelman M et al. (2014). Down Syndrome Phenotype in a Child with Partial Trisomy of Chromosome 21 and Paternally Derived Translocation t (20p; 21q) Gen Med (Los Angel). 2: 149-161. doi: 10.4172/2327-5146.1000149149.

Caloone J, Sanlaville D, Fichez A, Abel C, Huissoud C, Rudigoz RC. (2011). Trisomy 21 by isochromosome: a case report of true false negative of chorionic villi sampling. Gynecologie, obstetrique & fertilite. 39(12): e77-e80.; PMid:22079744

European Platform on Rare Disease Registration. (2023). URL:

Goncharenko G, Duderina Y, Synytsia Y, Galagan V, Kulbalaeva S. (2012). Down syndrome: frequency, diagnostics, medical-genetics consultation. Ukrainian Scientific Medical Youth Journal. 1(67): 45-48.

Gordienko IY, Velichko AV, Tarapurova ОМ, Nosko AO, Grebinichenko GO, Nikitchina TV. (2012). New prenatal ultrasound marker in the diagnosis of Down syndrome. Health of woman. 3 (69): 182-187.

Gordienko IYu, Nikitchina TV, Melnik YuМ, Tavokina LV, Vashchenko OO, Lucenko SV et al. (2018). A rare case of prenatally diagnosed deletion of chromosome 21 in the fetus with multiple anomalies. Clinical genetics and perinatal diagnostics. 1 (4): 54-58.

Kagan KO, Sonek J, Kozlowski P. (2022). Antenatal screening for chromosomal abnormalities. Archives of gynecology and obstetrics. 305(4): 825-835.; PMid:35279726 PMCid:PMC8967741

Kataguiri MR, Araujo Júnior E, Silva Bussamra LC, Nardozza LM, Fernandes Moron A. (2014). Influence of second-trimester ultrasound markers for Down syndrome in pregnant women of advanced maternal age. Journal of pregnancy: 785730.; PMid:24795825 PMCid:PMC3984820

Kennerknecht I, Barbi G, Djalali M, Mehnert K, Schneider M, Terinde R, Vogel W. (1998). False-negative findings in chorionic villus sampling. An experimental approach and review of the literature. Prenatal diagnosis. 18(12): 1276-1282.<1276::AID-PD445>3.0.CO;2-U

Kozlowski P, Burkhardt T, Gembruch U, Gonser M, Kähler C, Kagan KO et al. (2019). DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures. Empfehlungen der DEGUM, der ÖGUM, der SGUM und der FMF Deutschland zum Einsatz von Ersttrimester-Screening, früher Fehlbildungsdiagnostik, Screening an zellfreier DNA (NIPT) und diagnostischen Punktionen. Ultraschall in der Medizin. 40(2): 176-193.; PMid:30001568

Lyle R, Béna F, Gagos S, Gehrig C, Lopez G, Schinzel A et al. (2009). Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. European journal of human genetics : EJHG. 17(4): 454-466.; PMid:19002211 PMCid:PMC2986205

Mao S, Sun L, Tu M, Zou C, Wang X. (2015). Cytogenetic and Clinical Features in Children Suspected With Congenital Abnormalities in 1 Medical Center of Zhejiang Province From 2011 to 2014. Medicine. 94(42): e1857.; PMid:26496335 PMCid:PMC4620764

Marttala J, Kaijomaa M, Ranta J, Dahlbacka A, Nieminen P, Tekay A et al. (2012). False-negative results in routine combined first-trimester screening for down syndrome in Finland. American journal of perinatology. 29(3): 211-216.; PMid:21833895

Morris JK, Waters JJ, de Souza E. (2012). The population impact of screening for Down syndrome: audit of 19 326 invasive diagnostic tests in England and Wales in 2008. Prenatal diagnosis. 32(6): 596-601.; PMid:22573430

Papavassiliou P, Charalsawadi C, Rafferty K, Jackson-Cook C. (2015). Mosaicism for trisomy 21: a review. American journal of medical genetics. Part A. 167A(1): 26-39.; PMid:25412855

Park SY, Kim JW, Kim YM, Kim JM, Lee MH, Lee BY et al. (2001). Frequencies of fetal chromosomal abnormalities at prenatal diagnosis: 10 years experiences in a single institution. Journal of Korean medical science. 16(3): 290-293.; PMid:11410688 PMCid:PMC3054745

Pylyp LY, Spynenko LO, Verhoglyad NV, Mishenko AO, Mykytenko DO, Zukin VD. (2018). Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases. Journal of assisted reproduction and genetics. 35(2): 265-271.; PMid:29086320 PMCid:PMC5845039

Queremel Milani DA, Tadi P. (2023, Jan). Genetics, Chromosome Abnormalities. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. URL:

Ratanasiri T, Ratanasiri T, Komwilaisak R, Saksiriwuttho P. (2014). Second trimester genetic ultrasound for Down syndrome screening at Srinagarind Hospital. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 97 (10): S89-S96.

Roberson ED, Wohler ES, Hoover-Fong JE, Lisi E, Stevens EL, Thomas GH et al. (2011). Genomic analysis of partial 21q monosomies with variable phenotypes. European journal of human genetics: EJHG. 19(2): 235-238.; PMid:20823914 PMCid:PMC3025784

Society for Maternal-Fetal Medicine; Prabhu M, Kuller JA, Biggio JR. (2021). Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester. Society for Maternal-Fetal Medicine Consult Series #57. American journal of obstetrics and gynecology. 225(4): B2-B15.; PMid:34171388

Tsai S, Johal J, Malmsten J, Spandorfer S. (2023). Embryo ploidy in vitrified versus fresh oocytes: Is there a difference? Journal of assisted reproduction and genetics. 40(10): 2419-2425. Epub 2023 Aug 11. PMCID: PMC10504137.; PMid:37566316

Veropotvelyan MP, Shapovalenko LG, Savarovska OS. (2017). Incidence and spectrum of chromosomal abnormalities detected in married couples with early losses of pregnancy. REPRODUCTIVE ENDOCRINOLOGY. (35): 54-60.

Vlachadis N, Papadopoulou T, Vrachnis D, Manolakos E, Loukas N, Christopoulos P et al. (2023). Incidence and Types of Chromosomal Abnormalities in First Trimester Spontaneous Miscarriages: a Greek Single-Center Prospective Study. Maedica. 18(1): 35-41.; PMCid:PMC10231156

Wang Y, Zhu J, Chen Y, Lu S, Chen B, Zhao X et al. (2013). Two cases of placental T21 mosaicism: challenging the detection limits of non-invasive prenatal testing. Prenatal diagnosis. 33(12): 1207-1210.; PMid:23929588

Yildirim ME, Karakus S, Kurtulgan HK, Ozer L, Celik SB. (2023). Polyploidy Phenomenon as a Cause of Early Miscarriages in Abortion Materials. Balkan journal of medical genetics : BJMG. 26(1): 5-10.; PMid:37576791 PMCid:PMC10413878