Aneuploidy screening in women of advanced age in the public healthcare setting of a low- to middle- income country – an observational cohort study
DOI:
https://doi.org/10.7196/SAMJ.2025.v115i7.2052Keywords:
Down syndrome, Aneuploidy, Prenatal screening, LMIC, Africa, ultrasoundAbstract
Background. Screening and termination of pregnancy (TOP) for Down syndrome (DS) are both available in South Africa (SA), but DS is infrequently diagnosed prenatally in the public sector (7% in 2008), resulting in a high live-birth prevalence (1.33 - 2.1 per 1 000). In the SA public sector, DS screening and confirmatory genetic testing are fully state subsidised for women of advanced maternal age (AMA) but, owing to the low positive predictive value of AMA-based screening, ultrasound-based screening is also offered. Given the limited resources and the steady increase in the number of pregnant women of AMA, the value of DS screening in altering pregnancy outcome needs to be critically assessed.
Objectives. To determine the uptake of prenatal screening for DS, invasive testing and TOP in pregnant women of AMA, as well as factors influencing maternal decisions.
Methods. This retrospective cohort study, based on prospectively captured data, includes all women of AMA (>37 years at conception) seen at a regional fetal medicine unit in Cape Town offering fully state subsidised DS screening and testing for a geographically defined area, including mostly women of African or mixed ancestry. Screening was age- and ultrasound-based, and DS risks were calculated using published algorithms. Non-directive genetic counselling was provided to all women ≥40 years old (pre-screen if feasible), women with a relevant history, a fetal anomaly or DS risk higher than that of a woman aged 37 years. Participant characteristics, results, decisions and reasons to decline testing were recorded prospectively, and compared between women <40 completed years and ≥40 years old, and between women accepting or declining invasive testing or TOP.
Results. During the study period, 1 196 women of AMA were seen. Ninety-three received pre-screen counselling, and 44 of these declined DS screening (47.3% (95% confidence interval (CI) 36.9 - 57.9)). Uptake of invasive testing after screening was low (18.1% (CI 15.2 - 21.3)). Age category was not an independent confounder for this, but uptake was lower after previous miscarriage(s), higher after high-risk screening results and highest with a fetal anomaly. The most common reason for declining testing was opposition to TOP. The uptake of TOP for DS, when offered to those who were screened and had accepted invasive testing, was 65.8% (48.7 - 80.4).
Conclusion. The uptake of screening and/or testing was low, and this reflected strong views on TOP for DS. As uptake of testing and/or TOP was higher with abnormal ultrasound findings, a prenatal screening programme addressing structural anomalies and aneuploidies simultaneously (i.e. ultrasound) is preferred over other DS screening tools that target DS specifically.
References
1. Delport S, Christianson A, van den Berg H, Wolmarans L, Gericke G. Congenital anomalies in black South African liveborn neonates at an urban academic hospital. S Afr Med J 1995;85(1):11-15.
2. Al Mahri G, Nicolaides K. Evolution in screening for Down syndrome. Obstet Gynaecol 2019;21(1):51-57. https://doi.org/10.1111/tog.12534
3. American College of Obstetricians and Gynecologists. Screening for fetal chromosomal abnormalities: ACOG practice bulletin summary, number 226. Obs Gynecol 2020;136(4):859-867. https://doi. org/10.1097/AOG.0000000000004107
4. Audibert F, de Bie I, Johnson JA, et al. No. 348 – joint SOGC-CCMG guideline: Update on prenatal screening for fetal aneuploidy, fetal anomalies, and adverse pregnancy outcomes. J Obstet Gynaecol Canada 2017;39(9):805-817. https://doi.org/10.1016/j.jogc.2017.01.032
5. Chitayat D, Langlois S, Wilson RD. No. 261 – prenatal screening for fetal aneuploidy in singleton pregnancies. J Obstet Gynaecol Canada 2017;39(9):e380-394. https://doi.org/10.1016/j.jogc.2017.06.013 6. Baldus M. ‘Overestimated technology – underestimated consequences’ – reflections on risks, ethical
conflicts, and social disparities in the handling of non-invasive prenatal tests (NIPTs). Med Heal Care Philos 2023;26(2):271-282. https://doi.org/10.1007/s11019-023-10143-1
7. Reid B, Sinclair M, Barr O, Dobbs F, Crealey G. A meta-synthesis of pregnant women’s decision-making processes with regard to antenatal screening for Down syndrome. Soc Sci Med 2009;69(11):1561-1573. https://doi.org/10.1016/j.socscimed.2009.09.006
8. Kuppermann M, Norton ME, Gates E, Gregorich SE. Computerised prenatal genetic testing decision- assisting tool. Obs Gynecol 2009;113(1):53-63. https://doi.org/10.1097/AOG.0b013e31818e7ec4
9. Crombag NMTH, Boeije H, Iedema-Kuiper R, Schielen PCJI, Visser GHA, Bensing JM. Reasons for accepting or declining Down syndrome screening in Dutch prospective mothers within the context of national policy and healthcare system characteristics: A qualitative study. BMC Pregnancy Childbirth 2016;16(1):1-12. https://doi.org/10.1186/s12884-016-0910-3
10. Dahl K, Kesmodel U, Hvidman L, Olesen F. Informed consent: Attitudes, knowledge and information concerning prenatal examinations. Acta Obstet Gynecol Scand 2006;85(12):1414-1419. https://doi. org/10.1080/00016340600985164
11. Lawson K, Carlson K, Shynkaruk J. The portrayal of Down syndrome in prenatal screening information pamphlets. J Obs Gynaecol Can 2012;34(8):760-768. https://doi.org/10.1016/S1701-2163(16)35340-3
12. Wessels TM, Koole T, Penn C. ‘And then you can decide’ – antenatal foetal diagnosis decision-making
in South Africa. Heal Expect 2015;18(6):3313-3324. https://doi.org/10.1111/hex.12322
13. Lannoo L, van der Meij KRM, Bekker MN, et al. A cross-country comparison of pregnant women’s decision-making and perspectives when opting for non-invasive prenatal testing in the Netherlands
and Belgium. Prenat Diagn 2023;43(3):294-303. https://doi.org/10.1002/pd.6329
14. Molina F, Dehlendorf C, Gregorich S, Kupprmann M. Women’s preferences for and experiences with prenatal genetic testing decision making: Sociodemographic disparities in preference-concordant
decision making. Patient Educ Couns 2019;102(3):595-601. https://doi.org/10.1016/j.pec.2018.10.019
15. Pop-Tudose ME, Popescu-Spineni D, Armean P, Pop IV. Attitude, knowledge, and informed choice towards prenatal screening for Down Syndrome: A cross-sectional study. BMC Pregnancy Childbirth
2018;18(1):4-11. https://doi.org/10.1186/s12884-018-2077-6
16. Rowe H, Fisher J, Quinlivan J. Are pregnant Australian women well informed about prenatal genetic
screening? A systematic investigation using the Multidimensional Measure of Informed Choice. Aust
N Z J Obs Gynaecol 2006;46(5):433-439. https://doi.org/10.1111/j.1479-828X.2006.00630.x
17. Cho R, Plunkett B, Wolf M, Simon C, Grobman W. Health literacy and patient understanding of screening tests for aneuploidy and neural tube defects. Prenat Diagn 2007;27:463-467. https://.doi.
org/10.1002/pd.1712
18. Smith S, Sousa M, Essink-Bot M-L, Halliday J, Peate M, Fransen M. Socioeconomic differences in informed decisions about Down syndrome screening: A systematic review and research agenda. J Heal Commun 2016;21(8):868-907. https://doi.org/10.1080/10810730.2016.1177145
19. Geerts L. Prenatal diagnosis of chromosomal abnormalities in a resource-poor setting. Int J Gynecol Obstet 2008;103(1):16-21. https://doi.org/10.1080/10810730.2016.1177145
20. Urban MF, Stewart C, Ruppelt T, Geerts L. Effectiveness of prenatal screening for Down syndrome on the basis of maternal age in Cape Town. S Afr Med J 2011;101(1):45-48. https://doi.org/10.7196/samj.4188
21. Watcham S, Schön S, Christianson A. Neglect in the care of pregnant South African women of advanced maternal age. S Afr Med J 2007;97(11):1068-1069. https://doi.org/10.1002/pd.1220
22. Molteno C, Smart R, Viljoen D, Sayed R, Roux A. Twenty-year birth prevalence of Down syndrome in Cape Town, South Africa. Paediatr Perinat Epidemiol 1997;11(4):428-435. https://doi. org/10.1046/j.1365-3016.1997.d01-25.x
23. Binkert F, Mutter M, Schinzel A. Impact of prenatal diagnosis on the prevalence of live births with Down syndrome in the eastern half of Switzerland 1980 - 1996. Swiss Med Weekly 2002;132(33-34):478-484. https://doi.org/2002/33/smw-10009
24. Loane M, Morris JK, Addor M, et al. Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: Impact of maternal age and prenatal screening. Eur J Hum Genet 2013;21:27-33. https://doi.org/10.1038/ejhg.2012.94
25. Osterman MJK, Hamilton BE, Martin JA, Driscoll AK, Valenzuela CP. Births: Final data for 2020. Natl Vital Stat Reports 2022;70(17):1-49. https://www.cdc.gov/nchs/products/index.htm (accessed 8 November 2023).
26. Wu J, Morris JK. Trends in maternal age distribution and the live birth prevalence of Down’s syndrome in England and Wales: 1938 - 2010. Eur J Hum Genet 2013;21(9):943-947. https://doi.org/10.1038/ ejhg.2012.288
27. Hagen A, Entezami M, Gasiorek-Wiens A, et al. The impact of first trimester screening and early fetal anomaly scan on invasive testing rates in women with advanced maternal age. Ultraschall Med 2011;32(3):302-306. https://doi.org/10.1055/s-0029-1245560
28. Statistics South Africa. Statistical release P0305. Recorded live births, 2016. Pretoria: Stats SA, 2016. http://www.statssa.gov.za/publications/P0305/P03052016.pdf (accessed 26 June 2022).
29. Lo T, Lai K, Leung W, Lau W, Hung L, Tang R. A new policy for prenatal screening and diagnosis of Down syndrome for pregnant women with advanced maternal age in a public hospital. J Matern Fetal Neonatal Med 2010;23(8):914-919. https://doi.org/10.3109/14767050903370327
30. Petro G. Maternal mortality in Western Cape 2014 - 2016; data from Confidential Enquiry reporting system. Cape Town: Western Cape Government, 2017:1-21. https://www.westerncape.gov.za/assets/ departments/health/maternal_mortality_in_western_cape_2014-2016.pdf (accessed 29 June 2022).
31. Godino L, Turchetti D, Skirton H. A systematic review of factors influencing uptake of invasive fetal genetic testing by pregnant women of advanced maternal age. Midwifery 2013;29(11):1235-1243. https://doi.org/10.1016/j.midw.2012.11.009
32. Chervenak FA, McCullough LB. Ethical dimensions of first-trimester fetal aneuploidy screening. Clin Obstet Gynecol 2014;57(1):226-231. https://doi.org/10.1097/GRF.0000000000000014
33. Agathokleous M, Chaveeva P, Poon LCY, Kosinski P, Nicolaides KH. Meta-analysis of second-trimester markers for trisomy 21. Ultrasound Obstet Gynecol 2013;41(3):247-261. https://doi.org/10.1002/ uog.1236434
34. Cheng B-H, Chen J-H, Wang G-H. Psychological factors influencing choice of prenatal diagnosis in Chinese multiparous women with advanced maternal age. J Matern Fetal Neonatal Med 2019;32(14):2295-2301. https://doi.org/10.1080/14767058.2018.1432038
35. Van den Berg M, Timmermans D, Kleinveld J, Garcia E, van Vugt J, van der Wal G. Accepting or declining the offer of prenatal screening for congenital defects: Test uptake and women’s reasons. Prenat Diagn 2005;25(1):84-90. https://doi.org/10.1002/pd.1090
36. Wray AM, Ghidini A, Alvis C, Hodor J, Landy HJ, Poggi SH. The impact of first-trimester screening on AMA patients’ uptake of invasive testing. Prenat Diagn 2005;25(5):350-353. https://doi.org/10.1002/ pd.1144
37. Di Mattei V, Ferrari F, Perego G, Tobia V, Mauro F, Candiani M. Decision-making factors in prenatal testing: A systematic review. Heal Psychol Open 2021;8(1):1-20. https://doi.org/10.1177/2055102920987455
38. Heyman B, Hundt G, Sandall J, et al. On being at higher risk: A qualitative study of prenatal
screening for chromosomal anomalies. Soc Sci Med 2006;62(10):2360-2372. https://doi.org/10.1016/j.
socscimed.2005.10.018
39. Van der Meij KRM, Njio A, Martin L, et al. Routinisation of prenatal screening with the non-invasive prenatal test: Pregnant women’s perspectives. Eur J Hum Genet 2022;30(6):661-668. https://doi. org/10.1038/s41431-021-00940-8
40. ViljoenD,OosthuizenC,vanderWesthuizenS.Patientattitudestoprenatalscreeningandterminationof pregnancy at Groote Schuur Hospital: A two-year prospective study. East Afr Med J 1996;73(5):327-329.
41. Yeo L, Vintzileos AM. The use of genetic sonography to reduce the need for amniocentesis in women at high risk for Down syndrome. Semin Perinatol 2003;27(2):152-159. https://doi.org/10.1053/ sper.2003.50014
42. Darnes DR, Hashmi S, Monga M, et al. First-trimester screening and its impact on uptake of diagnostic testing. Prenat Diagn 2011;31(June):892-896. https://doi.org/10.1002/pd2800
43. Ilgin-Ruhi H, Yürür-Kutlay N, Tükün A, Bökesoy I. The role of genetic counselling on decisions of pregnant women aged 35 years or over regarding amniocentesis in Turkey. Eur J Med Genet 2005;48(1):13-19. https://doi.org/10.1016/j.ejmg.2005.01.018
44. Johnson J, Streets K, Fitsgeral J, Priest J, Vanisko M, Haag M. Influence of triple-marker screen risk versus a priori risk in decision for amniocentesis in women of advanced maternal age. Prenat Diagn 1998;18:979-986. https://doi.org/10.1007/BF01759617
45. Marini T, Sullivan J, Naeem R. Decisions about amniocentesis by advanced maternal age patients following maternal serum screening may not always correlate clinically with screening results: Need for improvement in informed consent process. Am J Med Genet 2002;109(3):171-175. https://doi. org/10.1002/ajmg.10319
46. Pinette MG, Garrett J, Salvo A, et al. Normal midtrimester (17 - 20 weeks) genetic sonogram decreases amniocentesis rate in a high-risk population. J Ultrasound Med 2001;20(6):639-644. https://doi. org/10.7863/jum.2001.20.6.639
47. Coory M, Roselli T, Carroll H. Antenatal care implications of population-based trends in Down syndrome birth rates by rurality and antenatal care provider, Queensland, 1990 - 2004. Med J Aust 2007;186(5):230-234. https://doi.org/10.5694/j.1326-5377.2007.tb00878.x
48. Muggli EE, McCloskey D, Halliday JL. Health behaviour modelling for prenatal diagnosis in Australia: A geodemographic framework for health service utilisation and policy development. BMC Health Serv Res 2006;6(109):1-10. https://doi.org/10.1186/1472-6963-6-109
49. Sadlecki P, Grabiec M, Walentowicz P, Walentowicz-Sadlecka M. Why do patients decline amniocentesis? Analysis of factors influencing the decision to refuse invasive prenatal testing. BMC Pregnancy Childbirth 2018;18(1):3-9. https://doi.org/10.1186/s12884-018-1812-3
50. Kuppermann M, Learman L, Gates E, et al. Beyond race or ethnicity and socioeconomic status: Predictors of prenatal testing for Down syndrome. Obs Gynecol 2006;107(5):1087-1097. https://doi. org/10.1097/01.AOG.0000214953.90248.db
51. Learman LA, Kuppermann M, Gates E, Nease RF, Gildengorin V, Washington AE. Social and familial context of prenatal genetic testing decisions: Are there racial/ethnic differences? Am J Med Genet Semin Med Genet 2003;119C(1):19-26. https://doi.org/10.1002/ajmg.c.10004
52. Bryant A, Norton M, Nakagawa S, et al. Variation in women’ s understanding of prenatal testing. Obs Gynecol 2016;125(6):1306-1312. https://doi.org/10.1097/AOG.0000000000000843
53. Nicolaides KH, Chervenak FA, McCullough LB, Avgidou K, Papageorghiou A. Evidence-based obstetric ethics, and informed decision-making by pregnant women about invasive diagnosis after first-trimester assessment of risk for trisomy 21. Am J Obstet Gynecol 2005;193(2):322-326. https:// doi.org/10.1016/j.ajog.2005.02.134
54. Lichtenbelt K, Schuring-Blom G, van der Burg N, et al. Factors determining uptake of invasive testing following first-trimester combined testing. Prenat Diagn 2013;33(4):328-333. https://doi.org/10.1002/ pd.4067
55. Baker D, Teklehaimanot S, Hassan R, Guze C. A look at a Hispanic and African American population in an urban prenatal diagnostic center: Referral reasons, amniocentesis acceptance, and abnormalities detected. Genet Med 2004;6(4):211-218. https://doi.org/10.1097/01.GIM.0000132684.94642.A0
56. Jaques A, Collins V, Muggli E, et al. Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome. Prenat Diagn 2010;30(6):522-530. https://doi.org/10.1002/pd.2509
57. Grinshpun-Cohen J, Miron-Shatz T, Rhee-Morris L, Briscoe B, Pras E, Towner D. A priori attitudes
predict amniocentesis uptake in women of advanced maternal age: A pilot study. J Heal Commun
2015;20(9):1107-1113. https://doi.org/10.1080/10810730.2015.1018632
58. Miltoft C, Wulff C, Kjærgaard S, Ekelund C, Tabor A, Danish Fetal Medicine Study Group. Parental
decisions about prenatal screening and diagnosis among infants with trisomy 21 in a national cohort with high uptake of combined first-trimester screening. Fetal Diagn Ther 2017;41(3):209-214. https:// doi.org/10.1159/000448093
59. Gil MM, Revello R, Poon LC, Akolekar R, Nicolaides KH. Clinical implementation of routine screening for fetal trisomies in the UK NHS: Cell-free DNA test contingent on results from first-trimester combined test. Ultrasound Obstet Gynecol 2016;47(1):45-52. https://doi.org/10.1002/uog.15783
60. Carroll JC, Brown JB, Reid AJ, Pugh P. Women’s experience of maternal serum screening. Can Fam Physician 2000;46(MAR):614-620. https://doi.org/10.1097/00006254-200101000-00012
61. Adiyaman D, Atakul B, Kuyucu M, Yildirim A, Pala H. Termination of pregnancy following a Down syndrome diagnosis: Decision-making process and influential factors in a Muslim but secular country, Turkey. J Perinat Med 2020;49(2):170-177. https://doi.org/10.1515/jpm-2020-0147
62. Kramer R, Jarve R, Aron Y, et al. Determinants of parental decisions after the prenatal diagnosis of Down syndrome. Am J Med Genet 1998;79(3):172-174. https://doi.org/10.1002/(sici)1096- 8628(19980923)79:3<172::aid-ajmg4>3.0.co;2-p
63. Perry S, Woodall A, Pressman E. Association of ultrasound findings with decision to continue Down syndrome pregnancies. Community Genet 2007;10(4):227-230. https://doi.org/10.1159/000106561 64. Weichert A, Braun T, Deutinger C, Henrich W, Kalache KD, Neymeyer J. Prenatal decision-making in
the second and third trimester in trisomy 21-affected pregnancies. J Perinat Med 2017;45(2):205-211.
https://doi.org/10.1515/jpm-2016-0108
65. Stewart C, Coetzee E. Attitudes of women to termination of pregnancy for fetal abnormality. Ultrasound Obstetr Gynecol 2010;36(S1):S281-S282. https://doi.org/10.1002/uog.8794
66. Malope MF, Stewart C, Fieggen KJ, Wessels TM. The decision-making process of pregnant individuals offered termination of pregnancy for serious congenital abnormalities. Patient Educ Couns 2023;112(March):107745. https://doi.org/10.1016/j.pec.2023.107745
67. Kluckow E, Halliday J, Poulton A, et al. Association between timing of diagnosis of trisomy 21, 18, and 13 and maternal socio-economic status in Victoria, Australia: A population-based cohort study from 2015 to 2016. Prenat Diagn 2019;39(13):1254-1261. https://doi.org/10.1002/pd.5577
68. Hunter AGW, Cappelli M, Humphreys L, et al. A randomised trial comparing alternative approaches to prenatal diagnosis counselling in advanced maternal age patients. Clin Genet 2005;67(4):303-313. https://doi.org/10.1111/j.1399-0004.2004.00405.x
69. Portocarrero M, Garvelink MM, Perez MMB, et al. Decision aids that support decisions about prenatal testing for Down syndrome: An environmental scan. BMC Med Inform Decis Making 2015;15(1):1-10. https://doi.org/10.1186/s12911-015-0199-6
70. Barr MD, Govender P, Rencken G. Raising a child with Down’s syndrome: Perspectives from South African urban care-givers. Afr Health Sci 2016;16(4):929-935. https://doi.org/10.4314/ahs.v16i4.7
71. Krzesinski EI, Geerts L, Urban MF. Neural tube defect diagnosis and outcomes at a tertiary South
African hospital with intensive case ascertainment. S Afr Med J 2019;109(9):698-703. https://doi. org/10.7196/SAMJ.2019.v109i9.13863
Downloads
Published
Issue
Section
License
Copyright (c) 2025 L Geerts, N Du Toit, M Schoeman
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Licensing Information
The SAMJ is published under an Attribution-Non Commercial International Creative Commons Attribution (CC-BY-NC 4.0) License. Under this license, authors agree to make articles available to users, without permission or fees, for any lawful, non-commercial purpose. Users may read, copy, or re-use published content as long as the author and original place of publication are properly cited.
Exceptions to this license model is allowed for UKRI and research funded by organisations requiring that research be published open-access without embargo, under a CC-BY licence. As per the journals archiving policy, authors are permitted to self-archive the author-accepted manuscript (AAM) in a repository.
Publishing Rights
Authors grant the Publisher the exclusive right to publish, display, reproduce and/or distribute the Work in print and electronic format and in any medium known or hereafter developed, including for commercial use. The Author also agrees that the Publisher may retain in print or electronic format more than one copy of the Work for the purpose of preservation, security and back-up.
