Intended for healthcare professionals


Prenatal screening for Down’s syndrome

BMJ 2009; 338 doi: (Published 13 February 2009) Cite this as: BMJ 2009;338:b140
  1. Zarko Alfirevic, professor of fetal and maternal medicine
  1. 1University of Liverpool, Liverpool Women’s Hospital, Liverpool L8 7SS
  1. zarko{at}

    A range of options that provide reliable and reproducible results is essential

    Screening for Down’s syndrome is the most controversial aspect of antenatal care offered to pregnant women, and it is a highly emotionally charged subject. In a recent editorial, two senior executives of Down Syndrome Education International claimed that current public health policies leading to an estimated annual loss of 400 normal fetuses to prevent the birth of 600 babies with Down’s syndrome were “shocking.”1 Both the estimated numbers and the tone of the statement were disputed by—among others—members of the editorial board of the journal published by Down Syndrome Education International.2

    Two BMJ papers provide additional information for the debate. In the first, Ekelund and colleagues (doi:10.1136/bmj.a2547) described real life data from Denmark after the introduction of the first trimester combined screening programme in 2005.3 In the second (doi:10.1136/bmj.b138), Gekas and colleagues calculated the cost effectiveness of 19 different screening algorithms using data generated by computer simulations.4

    Can prospective parents and clinicians make any sense of all this information? The language currently used to describe the evaluation of various screening policies is incomprehensible to most couples deciding whether or not the woman should be screened. Traditionally, a screening programme is deemed superior if the detection rate (sensitivity) is high and the false positive is rate is low. But these figures can be manipulated by using different “cut offs” for a screen positive result. A cut off of one in 300 may yield a high detection rate but will result in many unnecessary invasive procedures. Increasing a cut off to one in 100 means fewer false positive results, but also lower detection rates. In other words, somebody needs to decide what is more important to avoid—the unsuspected birth of a baby with Down’s syndrome or the loss of a healthy baby as a consequence of an invasive test (amniocentesis or chorionic villus sampling) triggered by a false positive test.

    Herein lies a problem. Can an individual make this judgment or is it the domain of policy makers in public health? The UK National Screening Committee has set the Down’s detection rate benchmark at 75%, with a false positive rate of less than 3%. It claims that four tests meet these criteria—the quadruple second trimester test, the serum first and second trimester integrated test, the full integrated test, and the first trimester combined test (table).5 From April 2010 the NHS target is even tougher—detection rate of more than 90% with a false positive rate of less than 2%.

    Glossary of the currently proposed screening tests for Down’s syndrome

    View this table:

    The Danish paper found that the first trimester combined test had a false positive rate of 3.3% (95% confidence interval 3.1% to 3.4%).3 Could the NHS can do better? Should we implement the integrated test (table 1) and “force” women to wait for the results until 16 weeks of gestation, or should we trust the Canadian data and implement contingency screening in the hope that everyday practice mirrors their modelled data?4

    In reality, prospective parents demand a personalised approach, entirely in keeping with the NHS’s promise of responsive, convenient, and personalised services.6 For antenatal Down’s syndrome screening, equal attention has to be given to women who choose not to be screened, those who think that any risk is unacceptable, and those who want a formal risk assessment to decide what to do.

    At any stage of the decision making process women are entitled to change their mind—specialists in this field see this on a daily basis. Women who decline Down’s syndrome screening often demand amniocentesis when Down’s syndrome is suspected on ultrasound later in pregnancy. Those who have Down’s syndrome detected on amniocentesis do not necessarily choose to terminate the pregnancy. Women who are screen positive often do not have confirmatory invasive testing and low risk women sometimes do. In Denmark in 2006, 1388 invasive procedures were triggered by a positive screening test but almost twice as many (n=2274) were carried out because of advanced maternal age or other indications. These decisions are not irrational—they are personal choices that change during pregnancy and between pregnancies. A risk of one in 50 may be reassuring for a 42 year old woman after a long period of infertility, whereas a risk of one in 500 may be unacceptable to a young woman with two healthy young children.

    The solution is not to search for a “one size fits all” screening test, but to have a range of options—all of which provide reliable and reproducible results. Worryingly, some reports have found that the quality of software used to calculate individualised risk varies greatly.7 The authorities should focus their attention on regulating and mandatory auditing of ultrasound and laboratory service providers, both in the NHS and the private sector. Prospective parents and their health carers should be allowed to decide what type of risk assessment (if any) they need, and how soon they want the results. More importantly, they do not need a cut off to tell them what to do.

    There is no such thing as a low risk or high risk for Down’s syndrome. All that we need is the woman’s own accurately and reproducibly determined pregnancy specific risk of Down’s syndrome, which—given the circumstances—may be acceptable or unacceptable to her. Surely a responsive and personalised NHS can cope with that.


    Cite this as: BMJ 2009;338:b140



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