Editing Down syndrome (section)

==Diagnosis==
===Screening before birth===
Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age.<ref name=ACOG2007/><ref>{{cite web|title=CG62: Antenatal care |url=http://publications.nice.org.uk/antenatal-care-cg62 |publisher=London: National Institute for Health and Clinical Excellence |access-date=16 February 2013 |author=National Institute for Health and Clinical Excellence |year=2008 |url-status=dead |archive-url=https://web.archive.org/web/20130126165543/http://publications.nice.org.uk/antenatal-care-cg62 |archive-date=26 January 2013 }}</ref> A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase the detection rate.<ref name=Hick2012/> None can be definitive; thus, if screening predicts a high possibility of Down syndrome, either [[amniocentesis]] or [[chorionic villus sampling]] is required to confirm the diagnosis.<ref name=ACOG2007/>

==== Ultrasound ====
[[Prenatal ultrasound]] can be used to screen for Down syndrome. Findings that indicate increased chances when seen at 14 to 24 weeks of [[gestation]] include a small or no nasal bone, [[ventriculomegaly|large ventricles]], [[nuchal fold thickness]], and an abnormal right [[subclavian artery]], among others.<ref name=Aga2013>{{cite journal | vauthors = Agathokleous M, Chaveeva P, Poon LC, Kosinski P, Nicolaides KH | title = Meta-analysis of second-trimester markers for trisomy 21 | journal = Ultrasound in Obstetrics & Gynecology | volume = 41 | issue = 3 | pages = 247–261 | date = March 2013 | pmid = 23208748 | doi = 10.1002/uog.12364 | doi-access = free }}</ref> The presence or absence of many markers is more accurate.<ref name=Aga2013/> Increased fetal [[nuchal translucency]] (NT) indicates an increased possibility of Down syndrome picking up 75–80% of cases and being falsely positive in 6%.<ref>{{cite journal | vauthors = Malone FD, D'Alton ME | title = First-trimester sonographic screening for Down syndrome | journal = Obstetrics and Gynecology | volume = 102 | issue = 5 Pt 1 | pages = 1066–1079 | date = November 2003 | pmid = 14672489 | doi = 10.1016/j.obstetgynecol.2003.08.004 | s2cid = 24592539 }}</ref>

<gallery mode="packed" heights="200px">
T21.JPG|Ultrasound of fetus with Down syndrome showing a [[megacystis|large bladder]]
Nuchal edema in Down Syndrome Dr. W. Moroder.jpg|Enlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndrome
</gallery>

====Blood tests====
Several blood markers can be measured to predict the chances of Down syndrome during the first or second trimester.<ref name=Can2012/><ref name=Deek2012/> Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results.<ref name=Can2012/> In the second trimester, often two or three tests are used in combination with two or three of: [[α-fetoprotein]], unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of cases.<ref name=Deek2012>{{cite journal | vauthors = Alldred SK, Deeks JJ, Guo B, Neilson JP, Alfirevic Z | title = Second trimester serum tests for Down's Syndrome screening | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 6 | pages = CD009925 | date = June 2012 | pmid = 22696388 | pmc = 7086392 | doi = 10.1002/14651858.CD009925 | url = http://eprints.nottingham.ac.uk/31499/1/Second%20trimester%20serum%20tests%20for%20Down%27s%20Syndrome%20screening.pdf | access-date = January 7, 2019 | url-status = dead | archive-url = https://web.archive.org/web/20191209234759/http://eprints.nottingham.ac.uk/31499/1/Second%20trimester%20serum%20tests%20for%20Down%27s%20Syndrome%20screening.pdf | archive-date = December 9, 2019 }}</ref>

Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester.<ref name="Mersy 318–29"/><ref>{{cite journal | vauthors = Verweij EJ, van den Oever JM, de Boer MA, Boon EM, Oepkes D | title = Diagnostic accuracy of noninvasive detection of fetal trisomy 21 in maternal blood: a systematic review | journal = Fetal Diagnosis and Therapy | volume = 31 | issue = 2 | pages = 81–86 | year = 2012 | pmid = 22094923 | doi = 10.1159/000333060 | doi-access = free }}</ref> The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high likelihood of trisomy 21.<ref name=Benn2011/> Accuracy has been reported at 98.6% in the first trimester of pregnancy.<ref name=Hick2012/> Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.<ref name=Benn2011>{{cite journal | vauthors = Benn P, Borrell A, Cuckle H, Dugoff L, Gross S, Johnson JA, Maymon R, Odibo A, Schielen P, Spencer K, Wright D, Yaron Y | display-authors = 6 | title = Prenatal Detection of Down Syndrome using Massively Parallel Sequencing (MPS): a rapid response statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis, 24 October 2011 | journal = Prenatal Diagnosis | volume = 32 | issue = 1 | pages = 1–2 | date = January 2012 | pmid = 22275335 | doi = 10.1002/pd.2919 | url = http://www.ispdhome.org/public/news/2011/ISPD_RapidResponse_MPS_24Oct11.pdf | url-status = dead | s2cid = 42116198 | archive-url = https://web.archive.org/web/20120319105150/http://www.ispdhome.org/public/news/2011/ISPD_RapidResponse_MPS_24Oct11.pdf | archive-date = 2012-03-19 }}</ref>

====Combinations====
{| class="wikitable"
|+ First- and second-trimester screening<ref name=ACOG2007>{{cite journal | title = ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities | journal = Obstetrics and Gynecology | volume = 109 | issue = 1 | pages = 217–227 | date = January 2007 | pmid = 17197615 | doi = 10.1097/00006250-200701000-00054 | author1 = ACOG Committee on Practice Bulletins }}</ref>
|-
!Screen
![[Gestational age (obstetrics)|Week of pregnancy]] when performed
!Detection rate
!False positive
!Description
|-
|Combined test
| 10–13.5&nbsp;wks
| 82–87%
| 5%
|Uses [[ultrasound]] to measure [[nuchal translucency]] in addition to blood tests for free or total beta-hCG and [[pregnancy-associated plasma protein A|PAPP-A]]
|-
|[[Quad screen]]
|15–20&nbsp;wks
|81%
| 5%
|Measures the maternal serum alpha-fetoprotein, unconjugated estriol, hCG, and [[inhibin]]-A
|-
|Integrated test
|15–20&nbsp;wks
|94–96%
|5%
|Is a combination of the quad screen, PAPP-A, and NT
|-
|[[Cell-free fetal DNA]]
|From 10&nbsp;wks<ref name=oxhp>{{cite web|title=Noninvasive prenatal diagnosis of fetal aneuploidy using cell-free fetal nucleic acids in maternal blood|url=https://www.oxhp.com/secure/policy/noninvasive_prenatal_diagnosis_fetal_aneuploidy.pdf|publisher=United Healthcare Oxford|access-date=25 March 2014|url-status=live|archive-url=https://web.archive.org/web/20140307093626/https://www.oxhp.com/secure/policy/noninvasive_prenatal_diagnosis_fetal_aneuploidy.pdf|archive-date=7 March 2014}}</ref>
|96–100%<ref name="Mersy 318–29">{{cite journal | vauthors = Mersy E, Smits LJ, van Winden LA, de Die-Smulders CE, Paulussen AD, Macville MV, Coumans AB, Frints SG | display-authors = 6 | title = Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012 | journal = Human Reproduction Update | volume = 19 | issue = 4 | pages = 318–329 | date = Jul–Aug 2013 | pmid = 23396607 | doi = 10.1093/humupd/dmt001 | doi-access = free }}</ref>
|0.3%<ref>{{cite journal | vauthors = Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, Craig JA, Chudova DI, Devers PL, Jones KW, Oliver K, Rava RP, Sehnert AJ | display-authors = 6 | title = DNA sequencing versus standard prenatal aneuploidy screening | journal = The New England Journal of Medicine | volume = 370 | issue = 9 | pages = 799–808 | date = February 2014 | pmid = 24571752 | doi = 10.1056/nejmoa1311037 | doi-access = free }}</ref>
|A blood sample is taken from the mother by [[venipuncture]] and is sent for DNA analysis.
|}

====Efficacy====
For combinations of ultrasonography and non-genetic blood tests, screening in both the first and second trimesters is better than just screening in the first trimester.<ref name=ACOG2007/> Common screening techniques in use are able to pick up 90–95% of cases, with a false-positive rate of 2–5%.<ref name=Can2012>{{cite journal | vauthors = Canick J | title = Prenatal screening for trisomy 21: recent advances and guidelines | journal = Clinical Chemistry and Laboratory Medicine | volume = 50 | issue = 6 | pages = 1003–1008 | date = June 2012 | pmid = 21790505 | doi = 10.1515/cclm.2011.671 | s2cid = 37417471 }}</ref> If Down syndrome occurs in one in 500 pregnancies with a 90% detection rate and the test used has a 5% false-positive rate, of 28 women who test positive on screening, only one will have a fetus with Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means of 11 women who test positive on screening, only one will have a fetus with Down syndrome.<ref name=Can2012/>

====Invasive genetic testing====
Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of [[miscarriage]] by between 0.5–1%.<ref name=Tab2010>{{cite journal | vauthors = Tabor A, Alfirevic Z | title = Update on procedure-related risks for prenatal diagnosis techniques | journal = Fetal Diagnosis and Therapy | volume = 27 | issue = 1 | pages = 1–7 | year = 2010 | pmid = 20051662 | doi = 10.1159/000271995 | doi-access = free | oclc = 23338607 }}</ref> The risk of limb problems may be increased in the offspring if chorionic villus sampling is performed before 10 weeks.<ref name=Tab2010/> 
[[File:Prenatal Down syndrome screening algorithm.png|thumb|An example of an algorithm for determining the indication for prenatal genetic testing of Down syndrome<ref>{{cite web|url=https://www.uptodate.com/contents/should-i-have-a-screening-test-for-down-syndrome-during-pregnancy-beyond-the-basics/print|title=Patient education: Should I have a screening test for Down syndrome during pregnancy? (Beyond the Basics)|website=UpToDate| vauthors = Halliday JV, Messerlian GM, Palomaki GE }}</ref>]]
The risk from the procedure is greater the earlier it is performed, thus amniocentesis is not recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational age.<ref name=Tab2010/>

===Abortion rates===
About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated.<ref name=Mans1999/> As a result, there is almost no one with Down syndrome in [[Iceland]] and [[Denmark]], where screening is commonplace.<ref name=Slate2018>{{Cite web|url=https://slate.com/human-interest/2018/05/how-down-syndrome-is-redefining-the-abortion-debate.html|title=How Down Syndrome Is Redefining the Abortion Debate| vauthors = Graham R |date=2018-05-31|website=Slate Magazine|language=en|access-date=2019-01-09}}</ref> In the United States, the termination rate after diagnosis is around 75%,<ref name=Slate2018/> but varies from 61 to 93%, depending on the population surveyed.<ref name=Nat2012/> Rates are lower among women who are younger and have decreased over time.<ref name=Nat2012/> When asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.<ref>{{cite journal | vauthors = Choi H, Van Riper M, Thoyre S | title = Decision making following a prenatal diagnosis of Down syndrome: an integrative review | journal = Journal of Midwifery & Women's Health | volume = 57 | issue = 2 | pages = 156–164 | date = Mar–Apr 2012 | pmid = 22432488 | doi = 10.1111/j.1542-2011.2011.00109.x | doi-access = free }}</ref>

===After birth===
A diagnosis can often be suspected based on the child's physical appearance at birth.<ref name=Nelson2011/> An analysis of the child's chromosomes is needed to confirm the diagnosis, and to determine if a [[Chromosomal translocation|translocation]] is present, as this may help determine the chances of the child's parents having further children with Down syndrome.<ref name=Nelson2011/>