• Efficiency of Prenatal Down Syndrome Diagnosis in the six oblasts of the south-east and central regions of Ukraine

Efficiency of Prenatal Down Syndrome Diagnosis in the six oblasts of the south-east and central regions of Ukraine

HEALTH OF WOMAN. 2017.4(120):20–30; doi 10.15574/HW.2017.120.20

Veropotvelyan N. P. 
The «Inter-provincial center of medical genetics and prenatal diagnosis», Krivoy Rog

Chromosomal aneuploidy (CA), having an incidence rate of 6-8 per 1000 live births, holds a special place in the structure of congenital and hereditary pathology. Among the common CA, trisomy 21 chromosomes (T21) is the most frequently found (its incidence rate in the general population amounts to 1:700–800 live births).

The objective: to study the efficiency of prenatal screening of CA (Down’s syndrome, DS) in the areas under the Center’s operational activity in the period of 2010-2015; To estimate the actual prevalence of DS in terms of born and prenatally diagnosed, eliminated fetuses with T21; On the basis of retrospective analysis of indications for prenatal karyotyping, in all detected cases of DS, to specify their structure and incidence rate; Based on data from medical literature, to make a comparative analysis with similar studies in different countries around the world.

Patients and methods. Over the six years (2010–2015) we have performed 3,137 invasive prenatal interventions, among which are 720 chorionic villus biopsies, 929 placententesises, and 1,488 amniocentesis of pregnant women having a high risk of CA, who were seeking medical help from our center whose operational activity covers 6 provinces (oblasts).

Results. From 3,137 prenatally karyotyped studies, there have been found only 558 cases of fetal CA, including 288 fetuses with T21.

A retrospective analysis of the structure of indications for invasive prenatal diagnosis in 288 pregnant women, having fetuses with prenatally detected DS, is presented as follows:

– separate: only 40-aged and above mothers – 4 (1.38%); Ultrasound (US)-findings (anomalies and markers of CA) – 192 (69.5%); High biochemical risk of CA – 2 (0.7%).

– combined: the mother’s age is 40 and above + US findings – 36 (13%); The mother’s age is 40 and above + US and biochemical (BC) markers – 8 (2.8%); Ultrasound findings + positive BC test – 32 (11.5%). Delivery of the previous child with DS by a pregnant woman under 40 years with no ultrasound and BC markers – 1 (0.34%).

In total, ultrasound findings (anomalies and markers of CA) were found in 97.5% of cases of prenatally detected fetuses with DS. The index of prenatal detection of fetuses with Down syndrome of all registered karyotyped cases of T21 (pre- and postnatal) in the Dnepropetrovskaya oblast corresponds to the average European level – 65%, (in the areas of the center’s operational activity – 37.7%). Taking into account 242 cases of DS in fetuses aborted prior 22 weeks of gestation, the actual prevalence of T21 in case of their birth would be 1:766 (13 per 10.000 infants).

Conclusions. Prevalence of Down syndrome among newborns in the Dnepropetrovskaya oblast as a result of prenatal diagnosis of chromosomal abnormalities makes 1: 1257, which is 1.8 times lower than the incidence in the average population (1:700); In other areas covered by the center’s consulting and diagnostic activity this rate is 1.1–1.55 times lower than that of the population one. In the absence of the existing system of prenatal diagnosis of Down syndrome, its average prevalence in these provinces would correspond to that of the general population 1:766 newborns.

Key words: сhromosomal abnormalities, Down syndrome, prenatal screening strategies, ultrasound diagnosis, invasive prenatal diagnosis, ultrasound markers.


1. Penrose LS. 1933. The relative effects of paternal and maternal age in mongolism. J Genet. 27:219-224. https://doi.org/10.1007/BF02984413

2. See https: //www. cdc. gov/ neddd/ birthdefects/downsyndrome.html

3. Wellesley D, Dolk H, Boyd PA, Greenlees R, Haeusler M et al. 2012. Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe. Eur J Hum Genet. 20(5):521–526. https://doi.org/10.1038/ejhg.2011.246; PMid:22234154 PMCid:PMC3330224

4. Hassold TJ, Jacobs PA. 1984. Trisomy in Man. Annual Review of Genetics. 18:69-97. https://doi.org/10.1146/annurev.ge.18.120184.000441; PMid:6241455

5. Morris JK, Wald NJ, Watt HC. 1999. Fetal loss in Down syndrome pregnancies. Prenat Diagn. 19(2):142-145. https://doi.org/10.1002/(SICI)1097-0223(199902)19:2<142::AID-PD486>3.3.CO;2-Z; https://doi.org/10.1002/(SICI)1097-0223(199902)19:2<142::AID-PD486>3.0.CO;2-7

6. Cuckle H. 1999. Down syndrome fetal loss rate in early pregnancy. Prenat Diagn. 19:1177-1179. https://doi.org/10.1002/(SICI)1097-0223(199912)19:12<1177::AID-PD714>3.0.CO;2-N

7. Benn PA, Egan JF. 2000. Survival of Down syndrome in utero. Prenat Diagn. 20(5):432-439. https://doi.org/10.1002/(SICI)1097-0223(200005)20:5<432::AID-PD819>3.0.CO;2-C

8. Baird PA, Sadovnick AD. 1987. Life expectancy in down syndrome. J.Pediatr. 110:849-854. https://doi.org/10.1016/S0022-3476(87)80395-5

9. Snijders RJ, Sundberg K, Holzgreve W, Henry G, Nickolaides KH. 1999. Maternal age and gestation-specific risk for trisomy 21. Ultrasound Obstet.Gynecol. 13:167-170. https://doi.org/10.1046/j.1469-0705.1999.13030167.x; PMid:10204206

10. Spencer K. 1999. Accuracy of Down’s syndrome risks produced in a prenatal screening program. Ann Clin Biochem. 36:101-103. https://doi.org/10.1177/000456329903600115; PMid:10370769

11. Wald NJ, Kennard A, Hackshaw A, McGuire A. 1997. Antenatal screening for Down’s syndrome. J Med Screen. 4(4):181-246. https://doi.org/10.1177/096914139700400402; PMid:9494915

12. Wald NJ, Cuckle HS, Densem JW, Kennard A, Smith D. 1992. Maternal serum screening for Down’s syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight. Br J Obstet Gynaecol. 99(2):144-149. https://doi.org/10.1111/j.1471-0528.1992.tb14474.x; PMid:1372820

13. Wald NJ, Densem JW, Smith D, Klee GG. 1994. Four-marker serum screening for Down’s syndrome. Prenat Diagn. 14(8):707-716. https://doi.org/10.1002/pd.1970140810; PMid:7527537

14. Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. 2003. 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. Br J Obstet Gynaecol. 110:281-286. https://doi.org/10.1046/j.1471-0528.2003.02246.x; https://doi.org/10.1046/j.1471-0528.2003.02222.x

15. Stenhouse EJ, Crossley JA, Aitken DA, Brogan K, Cameron AD, Connor JM. 2004. First-trimester combined ultrasound and biochemical screening for Down syndrome in routine clinical practice. Prenat Diagn. 24:774-780. https://doi.org/10.1002/pd.980; PMid:15503268

16. Khalil A, Pandya P. 2006. Screening for down syndrome. Br J Obstet Gynaecol India.3; 56:205-211.

17. Kuppermann M, Nease RF, Learman LA, Gates E, Blumberg B, Washington AE. 2000. Procedure-related miscarriages and Down syndrome-affected births: implications for prenatal testing based on women’s preferences. Obstet Gynecol. 96(4):511-516. https://doi.org/10.1016/S0029-7844(00)00969-8; https://doi.org/10.1097/00006250-200010000-00006; PMid:11004350

18. Alfirevic Z, Sundberg K, Brigham S. 2000. Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Database Syst Rev. (3):CD003252.

19. Nicolaides KH, Spencer K, Avgidou K, Faiola S, Falcon O. 2005. 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. 25(3):221-226. https://doi.org/10.1002/uog.1860; PMid:15736186

20. Kagan KO, Staboulidou I, Cruz J, Wright D, Nicolaides KH. 2010. Two-stage first-trimester screening for trisomy 21 by ultrasound assessment and biochemical testing. Ultrasound Obstet Gynecol. 36(5):542-547. https://doi.org/10.1002/uog.7663; PMid:20503223

21. Veropotvelyan NP. 2016. Sovremennyie vozmozhnosti prenatalnoy diagnostiki i meditsinyi ploda v Ukraine: stanovlenie, realii, problemyi i perspektivyi. Zhinochiy likar 1:54.

22. Zimmermann B. 2012. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenatal Diagnosis. 32:1233-1241. https://doi.org/10.1002/pd.3993; PMid:23108718 PMCid:PMC3548605

23. Nicolaides KH et al. 2013. Validation study of maternal blood cell-free DNA testing by targered sequencing of single-nucleotide polimorphisms at cromosomes 13,18,21,X and Y. Prenatal Diagnosis. 33:575-579. https://doi.org/10.1002/pd.4103; PMid:23613152

24. Veropotvelyan NP, Pogulyay YuS. 2015. Poslednie dostizheniya v oblasti neinvazivnoy prenatalnoy diagnostiki (NIPD/NIPT) i novyie strategii prenatalnogo skrininga hromosomnyih anomaliy. Prenatalnaya diagnostika. 14(2):101-110.

25. Spencer К. 2005. First trimester maternal serum screening for Down’s syndrome: evaluation of the DPC Immulite 2000 free Я-hCG and pregnancy-associated plasma protein-A assays. Ann Clin Biochem. 42:30-40. https://doi.org/10.1258/0004563053026880; PMid:15802030

26. Spencer К. 2003. Risk, a QC parameter. DSNEWS. 10(1):30.

27. Cuckle H. 2007. Coefficient of variance. DSNEWS. 14(2):25.

28. Urban MF, Stewart C, Ruppelt T, Geerts L. 2011. Effectiveness of prenatal screening for Down syndrome on the basis of maternal age in Cape Town. S Afr Med J. 101(1):45-48. https://doi.org/10.7196/SAMJ.4188; PMid:21626982

29. Larsen SO, Hansen J, Christiansen M, Nшrgaard-Pedersen B. 2002. Prenatal diagnosis of Down syndrome in Denmark 1980-1998 and future progress perspectives. Ugeskr Laeger. 23;164(39):4532-4536.

30. Ekelund CK, Jørgensen FS, Petersen OB, Sundberg K, Tabor A (Danish Fetal Medicine Research Group) 2008. Impact of a new national screening policy for Down’s syndrome in Denmark: population based cohort study. BMJ. 27;337:2547.

31. Jaques AM, Collins VR, Muggli EE, Amor DJ, Francis I, Sheffield LJ, Halliday JL. 2010. Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome. Prenat Diagn. 30(6):522-530. https://doi.org/10.1002/pd.2509

32. Rebhi F et al. 2014. Screening for Down syndrome. 13th World Congress in Fetal Medicine. PMCid:PMC4096094

33. Сhen Y, Qian X, Li J, Zhang J, Chu A, Schweitzer SO. 2007. Cost-effectiveness analysis of prenatal diagnosis intervention for Dow’n syndrome in China. Int J Technol Assess Health Care. 23(1):138-145. https://doi.org/10.1017/S0266462307051689; PMid:17234028

34. Šípek A, Gregor V, Љнpek A, Horбиek J, Calda P. First trimester combined test improved the performance of screening for trisomy 21; population data.Dep. Obst&Gynaec., First Faculty of Medicine and General Teaching Hospital, Charles University, Prague, Czech. 14th World Congress in Fetal Medicine

35. Wiechec M, Knafel A, Nocun A, Matyszkiewicz A, Juszczak M, Wiercinska E, Lataіa E. 2016. How Effective Is First-Trimester Screening for Trisomy 21 Based on Ultrasound Only?. Fetal Diagn Ther. 39(2):105-112. https://doi.org/10.1159/000434632; PMid:26303666

36. See http://www.eurocat-network. eu/prenatalscreeninganddiagnosis/prenataldetection(pd)rates

37. Bradford М. 2015. New Study: Abortion after Prenatal Diagnosis of Down Syndrome Reduces Down Syndrome Community by Thirty Percent 21.

38. See http: //www.cdc.gov/ncbddd/birthdefects/features/birthdefects-keyfindings.html

39. Jefferson T, Demicheli V, Mugford M. 2000. Elementary economic evaluation in health care. BMJ Books.

40. Odobo AO, Stamilo DM et al. 2006. A cost-effectiveness analysis of prenatal screening strategies for Down syndrome. Obstet.Gynecol. 107(1):209.

41. Beulen L, Grutters JP, Faas BH, Feenstra I, van Vugt JM, Bekker MN. 2014. The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis. Eur J Obstet Gynecol Reprod Biol. 182:53-61. https://doi.org/10.1016/j.ejogrb.2014.08.028; PMid:25238658

42. Nakaz MOZ Ukrainy vid 20.10.2015 № 685 «Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry syndromi Dauna».

43. Cuckle H. 2014. Screening for aneuploidies by cf DNA analysis of maternal blood-models for clinical implementation. Abstracts 13-th World Congressin FetaL Medicine (France Nice, 2014).

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