Optimal screening for Down syndrome: non invasive prenatal screening

Research output: Contribution to journalArticle

Abstract

Statistics from the World Health Organization on Downsyndrome estimate an effect size of 1:1000 to 1:1100live births each year (WHO, 2014). Recent UK statistics,produced from the National Cytogenetic Register (Morris etal 2014), report the rate 2.7:1000 births for babies born inEngland and Wales. They also report a significant increasein the proportion of women diagnosed prenatally, from45% in 2008 to 77% in 2012 for women under 35 years,and from 68% in 2008 to 80% for women over 35 in 2012.Historically, recognition of Down syndrome wasevidenced three centuries ago by Dr John Langdon Down,a medical doctor from Cornwall, who first described andclassified Down syndrome in 1862 under the label of a‘Mongolian idiot’ (Dunn, 1991). Today, it is the mostcommon chromosomal abnormality present at birth andhas become a major focus for prenatal screening worldwide.New screening technologies have made remarkable advancesin the past 15 years and this is most visible when we lookback at recommendations for the UK National ScreeningCommittee in 2001, which advised that all pregnant mothersshould be offered one of the available screening tests forDown syndrome. The committee recommended that by2007/2010 the screening tests should have a positive rate ofless than 3% and a detection rate of more than 75%. Majoradvances in screening technology have taken place since andthe American College of Medical Genetics and Genomics(ACMG, 2012) refer to the current gold standard antenatalscreening for Down syndrome as a combination of datafrom first trimester collected between 11 to 13 weeks +6days gestation, including assessment based on maternal age,ultrasound for nuchal translucency thickness and maternalserum analytes (free beta human chorionic gonadotrophinand pregnancy-associated plasma protein A). They reportthis assessment has 90% sensitivity and 95% specificity forpredicting Down syndrome.Technology has advanced rapidly and we have nextgenerationsequencing of circulating cell-free DNA inmaternal plasma capable of identifying nearly all Downsyndrome pregnancies with low false-positive rates basedon a single maternal blood test for non-invasive prenatalscreening for (Glen et al, 2012). The blood test is undertakenaround 10 weeks’ gestation and the results are availablewithin 10 to 14 days.The test costs between £99 and £800, depending on theprovider (currently available from medical staff in HarleyStreet London and independent diagnostic companies). It isnot free within the NHS at this time, but may become sofollowing the results of the NIHR funded UK study lookingspecifically at non-invasive prenatal testing (NIPT) forDown syndrome. The study is being led by the RAPID teamfrom Great Ormond Street in London and involves six siteswhere women who have a risk of a Down syndrome baby>1:1,000 will be offered NIPT. There is some persuasiveresearch evidence reporting NIPT tests have 100%sensitivity and 100% specificity (Zimmermann et al, 2012).However, amniocentesis or chorionic villus sampling is stillbeing performed for confirmatory diagnosis.Recent UK research explored NIPT preferences of 335women and 181 health professionals using discrete choiceexperiments (Hill et al, 2012). The results demonstratedpreference for ‘safe’ tests conducted early in pregnancy,with high accuracy. For women the key attribute was‘no risk of miscarriage, whereas for health professionals itwas accuracy’.In ten years, based on current knowledge of personalisedmedicine, epigenetics and values-based medicine, one canenvision a maternity service where optimal NIPT screeningfor Down syndrome and other chromosomal abnormalitieswill be incorporated into everyday antenatal care. Thetechnology used in NIPT can scan the entire genetic code ofthe fetus leading to the need for sound bioethical principlesto be put in place. The challenge for us as midwives is toremain committed to listening to the voices of the womenwe serve, while maintaining our professional, legal, moraland academic integrity in the midst of a sea of turbulentcultural and technological change.
LanguageEnglish
Pages111
JournalEvidence Based Midwifery
Volume12
Issue number4
Publication statusPublished - Dec 2014

Fingerprint

Down Syndrome
Prenatal Diagnosis
Pregnancy
Hematologic Tests
Parturition
Technology
Pregnancy-Associated Plasma Protein-A
Nuchal Translucency Measurement
Chorionic Villi Sampling
Genetic Code
Sensitivity and Specificity
Amniocentesis
Prenatal Care
Medical Staff
Wales
Maternal Age
Health
Midwifery
Spontaneous Abortion
First Pregnancy Trimester

Keywords

  • Down syndrome
  • screening
  • technology
  • non-invasive prenatal diagnosis and evidence based midwifery

Cite this

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title = "Optimal screening for Down syndrome: non invasive prenatal screening",
abstract = "Statistics from the World Health Organization on Downsyndrome estimate an effect size of 1:1000 to 1:1100live births each year (WHO, 2014). Recent UK statistics,produced from the National Cytogenetic Register (Morris etal 2014), report the rate 2.7:1000 births for babies born inEngland and Wales. They also report a significant increasein the proportion of women diagnosed prenatally, from45{\%} in 2008 to 77{\%} in 2012 for women under 35 years,and from 68{\%} in 2008 to 80{\%} for women over 35 in 2012.Historically, recognition of Down syndrome wasevidenced three centuries ago by Dr John Langdon Down,a medical doctor from Cornwall, who first described andclassified Down syndrome in 1862 under the label of a‘Mongolian idiot’ (Dunn, 1991). Today, it is the mostcommon chromosomal abnormality present at birth andhas become a major focus for prenatal screening worldwide.New screening technologies have made remarkable advancesin the past 15 years and this is most visible when we lookback at recommendations for the UK National ScreeningCommittee in 2001, which advised that all pregnant mothersshould be offered one of the available screening tests forDown syndrome. The committee recommended that by2007/2010 the screening tests should have a positive rate ofless than 3{\%} and a detection rate of more than 75{\%}. Majoradvances in screening technology have taken place since andthe American College of Medical Genetics and Genomics(ACMG, 2012) refer to the current gold standard antenatalscreening for Down syndrome as a combination of datafrom first trimester collected between 11 to 13 weeks +6days gestation, including assessment based on maternal age,ultrasound for nuchal translucency thickness and maternalserum analytes (free beta human chorionic gonadotrophinand pregnancy-associated plasma protein A). They reportthis assessment has 90{\%} sensitivity and 95{\%} specificity forpredicting Down syndrome.Technology has advanced rapidly and we have nextgenerationsequencing of circulating cell-free DNA inmaternal plasma capable of identifying nearly all Downsyndrome pregnancies with low false-positive rates basedon a single maternal blood test for non-invasive prenatalscreening for (Glen et al, 2012). The blood test is undertakenaround 10 weeks’ gestation and the results are availablewithin 10 to 14 days.The test costs between £99 and £800, depending on theprovider (currently available from medical staff in HarleyStreet London and independent diagnostic companies). It isnot free within the NHS at this time, but may become sofollowing the results of the NIHR funded UK study lookingspecifically at non-invasive prenatal testing (NIPT) forDown syndrome. The study is being led by the RAPID teamfrom Great Ormond Street in London and involves six siteswhere women who have a risk of a Down syndrome baby>1:1,000 will be offered NIPT. There is some persuasiveresearch evidence reporting NIPT tests have 100{\%}sensitivity and 100{\%} specificity (Zimmermann et al, 2012).However, amniocentesis or chorionic villus sampling is stillbeing performed for confirmatory diagnosis.Recent UK research explored NIPT preferences of 335women and 181 health professionals using discrete choiceexperiments (Hill et al, 2012). The results demonstratedpreference for ‘safe’ tests conducted early in pregnancy,with high accuracy. For women the key attribute was‘no risk of miscarriage, whereas for health professionals itwas accuracy’.In ten years, based on current knowledge of personalisedmedicine, epigenetics and values-based medicine, one canenvision a maternity service where optimal NIPT screeningfor Down syndrome and other chromosomal abnormalitieswill be incorporated into everyday antenatal care. Thetechnology used in NIPT can scan the entire genetic code ofthe fetus leading to the need for sound bioethical principlesto be put in place. The challenge for us as midwives is toremain committed to listening to the voices of the womenwe serve, while maintaining our professional, legal, moraland academic integrity in the midst of a sea of turbulentcultural and technological change.",
keywords = "Down syndrome, screening, technology, non-invasive prenatal diagnosis and evidence based midwifery",
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note = "Reference text: The American College of Medical Genetics and Genomics (ACMG 2013) . Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol 2012;120:1532-4. Dunn PM. (1991) Dr Langdon Down (1828-1896) and ‘mongolism’. Arch Dis Child. Jul 1991; 66 (7 Spec No): 827–828: PMCID: PMC1590233 Glenn E. Palomaki GE, Deciu C, Kloza EM et al (2012) DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study Genetics in Medicine (2012)14,296–305 doi:10.1038/gim.2011.73 Hill M, Fisher J, Chitty L, Morris S (2012) Women’s and health professionals’ preferences for prenatal tests for Down syndrome: a discrete choice experiment to contrast noninvasive prenatal diagnosis with current invasive tests Genetics in Medicine (2012) 14,905–913, doi:10.1038/gim.2012.68 Morris JK, Springett A (2014) The National Down Syndrome Cytogenetic Register for England and Wales 2012 Annual Report. Queen Mary University of London, Barts and The London School of Medicine and Dentistry. World health Organization (WHO) (2014) http://www.who.int/genomics/public/ geneticdiseases/en/index1.html accessed 15th November 2014. Zimmermann B, Hill M, Gemelos G, Demko Z, Banjevic M, Baner J, et al (2012) Non-invasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenatal Diagnosis 2012;32:1233-41.",
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Optimal screening for Down syndrome: non invasive prenatal screening. / Sinclair, M.

In: Evidence Based Midwifery, Vol. 12, No. 4, 12.2014, p. 111.

Research output: Contribution to journalArticle

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AU - Sinclair, M.

N1 - Reference text: The American College of Medical Genetics and Genomics (ACMG 2013) . Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol 2012;120:1532-4. Dunn PM. (1991) Dr Langdon Down (1828-1896) and ‘mongolism’. Arch Dis Child. Jul 1991; 66 (7 Spec No): 827–828: PMCID: PMC1590233 Glenn E. Palomaki GE, Deciu C, Kloza EM et al (2012) DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study Genetics in Medicine (2012)14,296–305 doi:10.1038/gim.2011.73 Hill M, Fisher J, Chitty L, Morris S (2012) Women’s and health professionals’ preferences for prenatal tests for Down syndrome: a discrete choice experiment to contrast noninvasive prenatal diagnosis with current invasive tests Genetics in Medicine (2012) 14,905–913, doi:10.1038/gim.2012.68 Morris JK, Springett A (2014) The National Down Syndrome Cytogenetic Register for England and Wales 2012 Annual Report. Queen Mary University of London, Barts and The London School of Medicine and Dentistry. World health Organization (WHO) (2014) http://www.who.int/genomics/public/ geneticdiseases/en/index1.html accessed 15th November 2014. Zimmermann B, Hill M, Gemelos G, Demko Z, Banjevic M, Baner J, et al (2012) Non-invasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenatal Diagnosis 2012;32:1233-41.

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N2 - Statistics from the World Health Organization on Downsyndrome estimate an effect size of 1:1000 to 1:1100live births each year (WHO, 2014). Recent UK statistics,produced from the National Cytogenetic Register (Morris etal 2014), report the rate 2.7:1000 births for babies born inEngland and Wales. They also report a significant increasein the proportion of women diagnosed prenatally, from45% in 2008 to 77% in 2012 for women under 35 years,and from 68% in 2008 to 80% for women over 35 in 2012.Historically, recognition of Down syndrome wasevidenced three centuries ago by Dr John Langdon Down,a medical doctor from Cornwall, who first described andclassified Down syndrome in 1862 under the label of a‘Mongolian idiot’ (Dunn, 1991). Today, it is the mostcommon chromosomal abnormality present at birth andhas become a major focus for prenatal screening worldwide.New screening technologies have made remarkable advancesin the past 15 years and this is most visible when we lookback at recommendations for the UK National ScreeningCommittee in 2001, which advised that all pregnant mothersshould be offered one of the available screening tests forDown syndrome. The committee recommended that by2007/2010 the screening tests should have a positive rate ofless than 3% and a detection rate of more than 75%. Majoradvances in screening technology have taken place since andthe American College of Medical Genetics and Genomics(ACMG, 2012) refer to the current gold standard antenatalscreening for Down syndrome as a combination of datafrom first trimester collected between 11 to 13 weeks +6days gestation, including assessment based on maternal age,ultrasound for nuchal translucency thickness and maternalserum analytes (free beta human chorionic gonadotrophinand pregnancy-associated plasma protein A). They reportthis assessment has 90% sensitivity and 95% specificity forpredicting Down syndrome.Technology has advanced rapidly and we have nextgenerationsequencing of circulating cell-free DNA inmaternal plasma capable of identifying nearly all Downsyndrome pregnancies with low false-positive rates basedon a single maternal blood test for non-invasive prenatalscreening for (Glen et al, 2012). The blood test is undertakenaround 10 weeks’ gestation and the results are availablewithin 10 to 14 days.The test costs between £99 and £800, depending on theprovider (currently available from medical staff in HarleyStreet London and independent diagnostic companies). It isnot free within the NHS at this time, but may become sofollowing the results of the NIHR funded UK study lookingspecifically at non-invasive prenatal testing (NIPT) forDown syndrome. The study is being led by the RAPID teamfrom Great Ormond Street in London and involves six siteswhere women who have a risk of a Down syndrome baby>1:1,000 will be offered NIPT. There is some persuasiveresearch evidence reporting NIPT tests have 100%sensitivity and 100% specificity (Zimmermann et al, 2012).However, amniocentesis or chorionic villus sampling is stillbeing performed for confirmatory diagnosis.Recent UK research explored NIPT preferences of 335women and 181 health professionals using discrete choiceexperiments (Hill et al, 2012). The results demonstratedpreference for ‘safe’ tests conducted early in pregnancy,with high accuracy. For women the key attribute was‘no risk of miscarriage, whereas for health professionals itwas accuracy’.In ten years, based on current knowledge of personalisedmedicine, epigenetics and values-based medicine, one canenvision a maternity service where optimal NIPT screeningfor Down syndrome and other chromosomal abnormalitieswill be incorporated into everyday antenatal care. Thetechnology used in NIPT can scan the entire genetic code ofthe fetus leading to the need for sound bioethical principlesto be put in place. The challenge for us as midwives is toremain committed to listening to the voices of the womenwe serve, while maintaining our professional, legal, moraland academic integrity in the midst of a sea of turbulentcultural and technological change.

AB - Statistics from the World Health Organization on Downsyndrome estimate an effect size of 1:1000 to 1:1100live births each year (WHO, 2014). Recent UK statistics,produced from the National Cytogenetic Register (Morris etal 2014), report the rate 2.7:1000 births for babies born inEngland and Wales. They also report a significant increasein the proportion of women diagnosed prenatally, from45% in 2008 to 77% in 2012 for women under 35 years,and from 68% in 2008 to 80% for women over 35 in 2012.Historically, recognition of Down syndrome wasevidenced three centuries ago by Dr John Langdon Down,a medical doctor from Cornwall, who first described andclassified Down syndrome in 1862 under the label of a‘Mongolian idiot’ (Dunn, 1991). Today, it is the mostcommon chromosomal abnormality present at birth andhas become a major focus for prenatal screening worldwide.New screening technologies have made remarkable advancesin the past 15 years and this is most visible when we lookback at recommendations for the UK National ScreeningCommittee in 2001, which advised that all pregnant mothersshould be offered one of the available screening tests forDown syndrome. The committee recommended that by2007/2010 the screening tests should have a positive rate ofless than 3% and a detection rate of more than 75%. Majoradvances in screening technology have taken place since andthe American College of Medical Genetics and Genomics(ACMG, 2012) refer to the current gold standard antenatalscreening for Down syndrome as a combination of datafrom first trimester collected between 11 to 13 weeks +6days gestation, including assessment based on maternal age,ultrasound for nuchal translucency thickness and maternalserum analytes (free beta human chorionic gonadotrophinand pregnancy-associated plasma protein A). They reportthis assessment has 90% sensitivity and 95% specificity forpredicting Down syndrome.Technology has advanced rapidly and we have nextgenerationsequencing of circulating cell-free DNA inmaternal plasma capable of identifying nearly all Downsyndrome pregnancies with low false-positive rates basedon a single maternal blood test for non-invasive prenatalscreening for (Glen et al, 2012). The blood test is undertakenaround 10 weeks’ gestation and the results are availablewithin 10 to 14 days.The test costs between £99 and £800, depending on theprovider (currently available from medical staff in HarleyStreet London and independent diagnostic companies). It isnot free within the NHS at this time, but may become sofollowing the results of the NIHR funded UK study lookingspecifically at non-invasive prenatal testing (NIPT) forDown syndrome. The study is being led by the RAPID teamfrom Great Ormond Street in London and involves six siteswhere women who have a risk of a Down syndrome baby>1:1,000 will be offered NIPT. There is some persuasiveresearch evidence reporting NIPT tests have 100%sensitivity and 100% specificity (Zimmermann et al, 2012).However, amniocentesis or chorionic villus sampling is stillbeing performed for confirmatory diagnosis.Recent UK research explored NIPT preferences of 335women and 181 health professionals using discrete choiceexperiments (Hill et al, 2012). The results demonstratedpreference for ‘safe’ tests conducted early in pregnancy,with high accuracy. For women the key attribute was‘no risk of miscarriage, whereas for health professionals itwas accuracy’.In ten years, based on current knowledge of personalisedmedicine, epigenetics and values-based medicine, one canenvision a maternity service where optimal NIPT screeningfor Down syndrome and other chromosomal abnormalitieswill be incorporated into everyday antenatal care. Thetechnology used in NIPT can scan the entire genetic code ofthe fetus leading to the need for sound bioethical principlesto be put in place. The challenge for us as midwives is toremain committed to listening to the voices of the womenwe serve, while maintaining our professional, legal, moraland academic integrity in the midst of a sea of turbulentcultural and technological change.

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