Down Syndrome: Antenatal Screening Mathematics, Ethics and Its Implementation in the UK


Antenatal screening for Down syndrome involves the application of noninvasive measurements (blood tests or ultrasound scanning) taken early in pregnancy to determine whether a foetus is likely to be affected by Down syndrome, to allow identification of a small proportion of pregnancies (usually up to 5%) in which to carry out an invasive diagnostic test (chorionic villus sampling or amniocentesis). Restriction of the invasive test is advisable because there is a risk of iatrogenic foetal loss as a result of the diagnostic test. New possibilities include analysis of free serum deoxyribonucleic acid to avoid invasive foetal sampling.

Although screening is possible, there remains some controversy over whether it should be done. The Eugenics history of the mid‐twentieth century should give pause for thought over the ethical under‐pinning of this ‘routine’ antenatal test.

Key Concepts:

  • It is possible to screen for foetal aneuploidies in early pregnancy by using a statistical model of normality, and a statistical model of affected pregnancies, from which a risk can be calculated. In future, it may be possible to directly analyse foetal DNA in maternal plasma to carry out the same function.

  • New screening methods using free DNA in serum may soon be introduced.

  • Screening programmes for genetics disease pose questions about medical ethics which are very difficult to answer.

Keywords: Down syndrome; screening; trisomy 21; alpha‐foetoprotein; human chorionic gonadotropin; unconjugated estriol; nuchal fold; ethics

Figure 1.

Population distributions for a‐fetoprotein (AFP) and human chorionic gonadotropin (HCG) for Down syndrome and ‘normal’ pregnancies, assuming equal incidence.

Figure 2.

Population distributions for a‐fetoprotein (AFP) and human chorionic gonadotropin (HCG) for Down syndrome and ‘normal’ pregnancies, with correct incidences. Note that the Down syndrome peak is now hidden by the ‘normal’ peak.

Figure 3.

Illustration to demonstrate how likelihood ratios are calculated.

Figure 4.

Effect of maternal age on screening. As age increases the potential for being identified as being at ‘high risk’ increases. AFP, a‐fetoprotein; HCG, human chorionic gonadotropin; MoM, multiple of the median.

Figure 5.

Age‐related false positive rate for Down syndrome (double) screening.

Figure 6.

Age‐related detection rate for Down syndrome (double) screening.



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Further Reading

Boston S (1994b) Too Deep for Tears: Eighteen Years After the Death of Will, My Son. London: Rivers Oram Press. ISBN 978–0044408918.

Glad J (2006) Future Human Evolution: Eugenics in the Twenty‐First Century. Schuylkill Haven, PA: Hermitage Books. ISBN 978–1557791542.

Grudzinskas JG, Chard T, Chapman M and Cuckle H (eds) (1994) Screening for Down's Syndrome. Cambridge: Cambridge University Press. ISBN 0–521–45271‐6.

Grudzinskas JG and Ward RHT (eds) (1997) Screening for Down Syndrome in the First Trimester. London: RCOG Press. ISBN 0–902331‐98‐1.

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Mackellar C and Bechtel C (eds) (2014) The Ethics of the New Eugenics. Oxford: Berghahn Books. ISBN 978‐1‐78238‐120‐4.

Reynolds T (2009) The ethics of antenatal screening: lessons from cnut. Clinical Biochemist Reviews 30: 187–196.

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Reynolds, Tim M(Aug 2014) Down Syndrome: Antenatal Screening Mathematics, Ethics and Its Implementation in the UK. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005635.pub3]