Barts and The London School of Medicine and Dentistry

Antenatal Screening for Down's Syndrome

Summary

Research at Barts and the London School of Medicine and Dentistry significantly improved the accuracy of antenatal screening for Down’s syndrome. The tests were developed by Professor Nick Wald’s team at Queen Mary’s Wolfson Institute of Preventive Medicine and were adopted as national UK policy in 2003 and remain an established gold standard worldwide. As a result, most Down’s syndrome babies in UK are now born through parental informed choice, and approximately 3,000 fewer babies with the syndrome were born between 2008 and 2013. Screening programmes in numerous countries are based on this research.

The science: developing tests to improve antenatal screening for Down’s syndrome

Down’s syndrome is the commonest genetic disorder in the UK. It produces moderate to severe mental impairment with or without physical abnormalities, as well as early-onset dementia. Almost all individuals with this syndrome require lifelong care. Down’s syndrome affects one in 500 fetuses in mothers under 20 years’ old but rises sharply with maternal age in mothers over 45. Over 90% of couples choose to terminate a pregnancy if they know their fetus is affected. Those who choose not to terminate prefer to know the diagnosis in advance of the birth. No non-invasive test yet allows diagnosis of Down’s syndrome at a sufficiently early stage of pregnancy to offer the choice of termination with 100% accuracy, while invasive tests and carry a risk of miscarriage and fetal harm. False negative and false positive tests place significant stress on the couple and have ethical implications.

Research at Queen Mary was based on data collected from 25 maternity units on 47,053 singleton pregnancies in 1999-2002, including 101 with Down’s syndrome, and compared five tests or test combinations, of which the Integrated test (first and second trimester tests combined in a single estimate, which detects over 90% of Down’s fetuses with a 2% false positive rate) was the most accurate; but the first-trimester Combined test (involving only a single visit) had better cost-effectiveness. In a national audit of almost 11,000 pregnant women through the National Down Syndrome Cytogenetic Register: 98% of women accepted the Integrated test and of these, 94% completed both stages of the test.

Putting research into action: impact on health and information for patients

NICE Guidance 2008 (updated from 2003): recommendations were based on SURUSS and subsequent work undertaken by Queen Mary researchers and others, and recommended Combined test for women presenting before 15 weeks and that patients should be given accurate information about detection and false positive rates. Training and professional development for midwives has been provided by the Wolfson Institute at Queen Mary in the form of study days. A total of 34 study days have been held from 2008 to 2013, with over 500 midwives attending. The proportion of Down’s cases diagnosed antenatally in UK rose from 30.6% in 1989-90 to 60.3% in 2008-9 and has remained at over 60% in 2008-13.

The advances in screening practice have been shown to be cost effective and led to overall economic savings. For example, that to screen 100,000 women, the second trimester double test was estimated to cost £5.8 million at a 90% detection rate, compared with £4.6 million for the Combined test and £3.0 million for the Integrated test.

The European Union EUROCAT (European Surveillance of Congenital Abnormalities) programme report 2010 suggests that the research findings have influenced current antenatal screening policy in Croatia, Denmark, Finland, France, Italy, Netherlands, Spain, and Switzerland.