Editing Prenatal testing (section)

==By invasiveness==
[[File:Amniocentesis.png|thumb|220x220px|Amniocentesis is an example of an invasive diagnostic prenatal test.]]
Diagnostic prenatal testing can be performed by [[invasive (medical)|invasive]] or [[Non-invasive (medical)|non-invasive]] methods. An invasive method involves probes or needles being inserted into the [[uterus]], e.g. [[amniocentesis]], which can be done from about 14 weeks gestation, and usually up to about 20 weeks, and [[chorionic villus sampling]], which can be done earlier (between 9.5 and 12.5 weeks gestation) but which may be slightly more risky to the fetus. One study comparing transabdominal chorionic villus sampling with second trimester amniocentesis found no significant difference in the total pregnancy loss between the two procedures.<ref name="Alfirevic">[https://web.archive.org/web/20121024062959/http://apps.who.int/rhl/reviews/langs/CD003252.pdf Amniocentesis and chorionic villus sampling for prenatal diagnosis (Review)]. By Alfirevic Z, Mujezinovic F, Sundberg K at [[The Cochrane Collaboration]], 2009</ref> However, [[Chorionic villus sampling|transcervical]] chorionic villus sampling carries a significantly higher risk, compared with a second-trimester amniocentesis, of total pregnancy loss ([[relative risk]] 1.40; 95% [[confidence interval]] 1.09 to 1.81) and spontaneous miscarriage (9.4% risk; relative risk 1.50; 95% confidence interval 1.07 to 2.11).<ref name="Alfirevic" />
[[File:Obsteric ultrasonograph.jpg|thumb|Ultrasonography is an example of a non-invasive diagnostic prenatal test.]]
Non-invasive techniques include examinations of the woman's womb through [[ultrasonography]] and maternal serum screens (i.e. [[Alpha-fetoprotein]]). Blood tests for select trisomies (Down syndrome in the United States, Down and Edwards syndromes in China) <!-- as of October 2011 --> based on detecting [[cell-free placental DNA]] present in maternal blood, also known as non-invasive prenatal testing (NIPT), have become available.<ref name="Palomaki">{{cite journal | vauthors = Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA | display-authors = 6 | title = DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study | journal = Genetics in Medicine | volume = 13 | issue = 11 | pages = 913–20 | date = November 2011 | pmid = 22005709 | doi = 10.1097/GIM.0b013e3182368a0e | s2cid = 24761833 | doi-access = free }}</ref> If an elevated risk of chromosomal or genetic abnormality is indicated by a non-invasive screening test, a more invasive technique may be employed to gather more information.<ref name="ISPD">{{Citation
 |vauthors=Benn P, Borrell A, Cuckle H, Dugoff L, Gross S, Johnson J, Maymon R, Odibo A, Schielen P, Spencer K, Wright D, Yaron Y
 |date = October 24, 2011
|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
 |work = ISPD rapid response statement
 |publisher = International Society for Prenatal Diagnosis
 |place = Charlottesville, VA
 |url = http://www.ispdhome.org/public/news/2011/ISPD_RapidResponse_MPS_24Oct11.pdf
 |archive-url = https://web.archive.org/web/20120319105150/http://www.ispdhome.org/public/news/2011/ISPD_RapidResponse_MPS_24Oct11.pdf
 |url-status = dead
 |archive-date = March 19, 2012
|access-date = October 25, 2011
}}</ref> In the case of neural tube defects, a detailed ultrasound can non-invasively provide a definitive diagnosis.{{citation needed|date=February 2022}}

One of the major advantages of the non-invasive prenatal testing is that the chance of a false positive result is very low. This accuracy is very important for the pregnant woman, as due to a high sensitivity and specificity of the testing, especially for Down syndrome, the invasive testing could be avoided, which includes the risk of a miscarriage.<ref>{{Cite journal|last1=Taylor-Phillips|first1=Sian|last2=Freeman|first2=Karoline|last3=Geppert|first3=Julia|last4=Agbebiyi|first4=Adeola|last5=Uthman|first5=Olalekan A.|last6=Madan|first6=Jason|last7=Clarke|first7=Angus|last8=Quenby|first8=Siobhan|last9=Clarke|first9=Aileen|date=January 1, 2016|title=Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis|url=https://bmjopen.bmj.com/content/6/1/e010002|journal=BMJ Open|language=en|volume=6|issue=1|pages=e010002|doi=10.1136/bmjopen-2015-010002|issn=2044-6055|pmid=26781507|pmc=4735304}}</ref><ref>{{Cite journal|last1=Allyse|first1=Megan|last2=Minear|first2=Mollie A|last3=Berson|first3=Elisa|last4=Sridhar|first4=Shilpa|last5=Rote|first5=Margaret|last6=Hung|first6=Anthony|last7=Chandrasekharan|first7=Subhashini|date=January 16, 2015|title=Non-invasive prenatal testing: a review of international implementation and challenges|journal=International Journal of Women's Health|volume=7|pages=113–126|doi=10.2147/IJWH.S67124|issn=1179-1411|pmc=4303457|pmid=25653560 |doi-access=free }}</ref>

=== Testing guidelines and qualifying risk factors for invasive testing ===
The American College of Obstetricians and Gynecologists ([[American College of Obstetricians and Gynecologists|ACOG]]) guidelines currently recommend that anyone who is pregnant, regardless of age, should discuss and be offered non-invasive prenatal genetic screening and diagnostic testing options.<ref>{{Cite web |title=Current ACOG Guidance |url=https://www.acog.org/en/advocacy/policy-priorities/non-invasive-prenatal-testing/current-acog-guidance |access-date=2022-09-12 |website=www.acog.org |language=en}}</ref> Non-invasive prenatal genetic screening is typically performed at the end of the 1st trimester (11–14 weeks) or during the beginning of the second trimester (15–20 weeks). This involves the pregnant woman receiving a blood draw with a needle and a syringe and an ultrasound of the fetus. Screening tests can then include serum analyte screening or [[cell-free fetal DNA]], and [[Nuchal scan|nuchal translucency ultrasound]] [NT], respectively.<ref>{{Citation |last1=Gordon |first1=Shaina |title=Prenatal Genetic Screening |date=2022 |url=http://www.ncbi.nlm.nih.gov/books/NBK557702/ |work=StatPearls |access-date=2022-09-19 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491634 |last2=Langaker |first2=Michelle D.}}</ref> It is important to note that screening tests are not diagnostic, and concerning screening results should be followed up with invasive diagnostic testing for a confirmed diagnosis. Invasive diagnostic prenatal genetic testing can involve chronic villus sampling (CVS) or [[amniocentesis]].<ref name="Ghi 256–268">{{Cite journal |last1=Ghi |first1=T. |last2=Sotiriadis |first2=A. |last3=Calda |first3=P. |last4=Da Silva Costa |first4=F. |last5=Raine-Fenning |first5=N. |last6=Alfirevic |first6=Z. |last7=McGillivray |first7=G. |last8=International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) |date=August 2016 |title=ISUOG Practice Guidelines: invasive procedures for prenatal diagnosis: ISUOG Guidelines |journal=Ultrasound in Obstetrics & Gynecology |language=en |volume=48 |issue=2 |pages=256–268 |doi=10.1002/uog.15945 |pmid=27485589 |s2cid=35587941 |doi-access=free|hdl=11343/291569 |hdl-access=free }}</ref> The ACOG recommends genetic screening before pregnancy to all pregnant women planning to have a family.<ref>{{cite journal |date=March 2017 |title=Committee Opinion No. 690 Summary: Carrier Screening in the Age of Genomic Medicine |journal=Obstetrics and Gynecology |volume=129 |issue=3 |pages=595–596 |doi=10.1097/AOG.0000000000001947 |pmid=28225420 |s2cid=205468921}}</ref> After comprehensive counseling and discussion that acknowledges residual risks, it is important to respect the patients' right of choosing whether or not to pursue any component of genetic testing.{{citation needed|date=October 2022}}

The following are some reasons why a woman might consider her risk of birth defects already to be high enough to warrant skipping screening and going straight for invasive testing:<ref name="Ghi 256–268" />
* Increased risk of fetal aneuploidy based on personal obstetric history or family history affected by aneuploidy
* Increased risk for a known genetic or biochemical disease of the fetus
* Maternal transmissible infectious disease such as rubella or toxoplasma
* Parental request in the context of acute parental anxiety or under exceptional circumstances

====Patient acceptance====
Research was conducted to determine how women felt about noninvasive diagnosis of fetal aneuploid using maternal blood. This study was conducted using surveys. It was reported that eighty-two percent of pregnant women and seventy-nine percent of female medical students view this type of diagnosis in a positive light, agreeing that it is important for prenatal care. Overall, women responded optimistically that this form of diagnosis will be available in the future.<ref name="Ref5">{{cite journal |vauthors=Kooij L, Tymstra T, van den Berg P |date=February 2009 |title=The attitude of women toward current and future possibilities of diagnostic testing in maternal blood using fetal DNA |url=https://www.rug.nl/research/portal/en/publications/the-attitude-of-women-toward-current-and-future-possibilities-of-diagnostic-testing-in-maternal-blood-using-fetal-dna(37f11789-ccb4-42c7-aefb-60add0f166d5).html |journal=Prenatal Diagnosis |volume=29 |issue=2 |pages=164–8 |doi=10.1002/pd.2205 |pmid=19180577 |s2cid=7927318 |hdl=11370/37f11789-ccb4-42c7-aefb-60add0f166d5}}</ref>

{| class="wikitable plainrowheaders"
|+ Testing methods, by invasiveness
! scope="col" | Invasiveness
! scope="col" | Test
! scope="col" | Comments
! scope="col" | Time
|-
! scope="row" | Non-invasive
| [[Preimplantation genetic diagnosis]] (PGD)
| During [[in vitro fertilization]] (IVF) procedures, it is possible to sample cells from [[human embryo]]s before implantation.<ref>[http://www.inciid.org/article.php?cat=&id=362 Santiago Munne] {{Webarchive|url=https://web.archive.org/web/20140102193321/http://www.inciid.org/article.php?cat=&id=362 |date=January 2, 2014}}, ''INCIID'' – accessed July 18, 2009</ref> PGD is in itself non-invasive, but IVF usually involves invasive procedures such as [[transvaginal oocyte retrieval]]
| before implantation
|-
! scope="row" | Non-invasive
| External examination
| Examination of the woman's [[uterus]] from outside the body. The uterus is commonly palpated to determine if there are problems with the position of the fetus (i.e. [[Breech birth|breech position]]). [[Fundal height]] may also be measured.
| Second or third trimester
|-
! scope="row" | Non-invasive
| [[Obstetric ultrasonography|Ultrasound detection]]
| Commonly ''dating scans'' (sometimes known as ''booking scans or [[dating ultrasound]]s'') from 7 weeks to confirm pregnancy dates and look for [[Multiple birth|multiple pregnancies]]. The specialised [[nuchal scan]] at 11–13 weeks may be used to identify higher risks of Downs syndrome. Later ''morphology scans,'' also called ''[[anatomy ultrasound]]'', from 18 weeks may check for any abnormal development. Additional ultrasounds may be performed if there are any other problems with the pregnancy, or if the pregnancy is [[Postterm pregnancy|post-due]].
| First or second trimester
|-
! scope="row" | Non-invasive
| Fetal heartbeat
| Listening to the fetal heartbeat via an external monitor placed on the outside of the abdomen.
| First or second trimester
|-
! scope="row" | Non-invasive
| [[Non-stress test]]
| Use of [[cardiotocography]] during the third trimester to monitor fetal wellbeing.
| Third trimester
|-
! scope="row" | Non-invasive
| Maternal blood pressure
| Used to screen for [[pre-eclampsia]] throughout the pregnancy.
| First, second and third trimester
|-
! scope="row" | Non-invasive
| Maternal weighing
| Unusually low or high maternal weight can indicate problems with the pregnancy.
| First, second and third trimesters.
|-
! scope="row" | Less invasive
| Fetal cells in maternal blood (FCMB)<ref name="pmid11260204">{{cite journal | vauthors = Wachtel SS, Shulman LP, Sammons D | title = Fetal cells in maternal blood | journal = Clinical Genetics | volume = 59 | issue = 2 | pages = 74–9 | date = February 2001 | pmid = 11260204 | doi = 10.1034/j.1399-0004.2001.590202.x | s2cid = 10998402}}</ref>
| Requires a maternal blood draw. Based on enrichment of fetal cells which circulate in maternal blood. Since fetal cells hold all the genetic information of the developing fetus, they can be used to perform prenatal diagnosis.<ref>{{cite journal | vauthors = Herzenberg LA, Bianchi DW, Schröder J, Cann HM, Iverson GM | title = Fetal cells in the blood of pregnant women: detection and enrichment by fluorescence-activated cell sorting | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 76 | issue = 3 | pages = 1453–5 | date = March 1979 | pmid = 286330 | pmc = 383270 | doi = 10.1073/pnas.76.3.1453 | bibcode = 1979PNAS...76.1453H | doi-access = free}}</ref>
| First trimester
|-
! scope="row" | Less invasive
| [[Cell-free fetal DNA]] in maternal blood
|Requires a maternal blood draw. Based on DNA of fetal origin circulating in the maternal blood. Testing can potentially identify fetal [[aneuploidy]]<ref name="urlFetal DNA from Maternal Blood">{{cite journal | vauthors = Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR | title = Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 42 | pages = 16266–71 | date = October 2008 | pmid = 18838674 | pmc = 2562413 | doi = 10.1073/pnas.0808319105 | bibcode = 2008PNAS..10516266F | doi-access = free}}</ref> (available in the United States, beginning 2011) and gender of a fetus as early as six weeks into a pregnancy. Fetal DNA ranges from about 2–10% of the total DNA in maternal blood.

Cell-free fetal DNA also allows [[whole genome sequencing]] of the fetus, thus determining the complete [[DNA]] sequence of every gene.<ref>{{cite journal | vauthors = Yurkiewicz IR, Korf BR, Lehmann LS | title = Prenatal whole-genome sequencing—is the quest to know a fetus's future ethical? | journal = The New England Journal of Medicine | volume = 370 | issue = 3 | pages = 195–7 | date = January 2014 | pmid = 24428465 | doi = 10.1056/NEJMp1215536 | s2cid = 205109276 }}</ref>
| First trimester
|-
! scope="row" | Less invasive
| [[Glucose tolerance test]]ing
| Requires a maternal blood draw. Used to screen for [[gestational diabetes]].
| Second trimester
|-
! scope="row" | Less invasive
| [[Chorionic villus sampling|Transcervical]] retrieval of [[trophoblast cell]]s
| [[Cervical mucus aspiration]], [[cervical swabbing]], and [[cervical lavage|cervical]] or [[intrauterine lavage]] can be used to retrieve trophoblast cells for diagnostic purposes, including [[prenatal genetic analysis]]. Success rates for retrieving fetal trophoblast cells vary from 40% to 90%.<ref name="imudia" /> It can be used for [[fetal sex determination]] and identify [[aneuploidies]].<ref name="imudia" /> [[Antibody marker]]s have proven useful to select trophoblast cells for genetic analysis and to demonstrate that the abundance of recoverable trophoblast cells diminishes in abnormal gestations, such as in [[ectopic pregnancy]] or [[anembryonic gestation]].<ref name="imudia">{{cite journal | vauthors = Imudia AN, Kumar S, Diamond MP, DeCherney AH, Armant DR | title = Transcervical retrieval of fetal cells in the practice of modern medicine: a review of the current literature and future direction | journal = Fertility and Sterility | volume = 93 | issue = 6 | pages = 1725–30 | date = April 2010 | pmid = 20056202 | pmc = 2847626 | doi = 10.1016/j.fertnstert.2009.11.022}}</ref>
| First trimester<ref name="imudia" />
|-
! scope="row" | Less invasive
| Maternal serum screening
| Including β-[[human chorionic gonadotropin|hCG]], [[Pregnancy-associated plasma protein A|PAPP-A]], [[alpha fetoprotein]], inhibin-A.
| First or second trimester
|-
! scope="row" | More invasive
| [[Chorionic villus sampling]]
| Involves getting a sample of the [[chorionic villus]] and testing it. This can be done earlier than amniocentesis, but may have a higher risk of miscarriage, estimated at 1%.
| After 10 weeks
|-
! scope="row" | More invasive
| [[Amniocentesis]]
| This can be done once enough [[amniotic fluid]] has developed to sample. Cells from the fetus will be floating in this fluid, and can be separated and tested. Miscarriage risk of amniocentesis is commonly quoted as 0.06% (1:1600).<ref>{{cite journal | vauthors = Wilson RD, Langlois S, Johnson JA | title = Mid-trimester amniocentesis fetal loss rate | journal = Journal of Obstetrics and Gynaecology Canada | volume = 29 | issue = 7 | pages = 586–590 | date = July 2007 | pmid = 17623573 | doi = 10.1016/S1701-2163(16)32501-4 | url = http://sogc.org/wp-content/uploads/2013/01/gui194CPG0707.pdf | author4 = SOGC GENETICS COMMITTEE | author5 = CCMG PRENATAL DIAGNOSIS COMMITTEE | access-date = July 15, 2015 | archive-url = https://web.archive.org/web/20170810105511/https://sogc.org/wp-content/uploads/2013/01/gui194CPG0707.pdf | archive-date = August 10, 2017 | url-status = dead}}</ref> By [[amniocentesis]] it is also possible to [[cryopreserve]] [[amniotic stem cells]].<ref name="urlEuropean Biotech Company Biocell Center Opens First U.S. Facility for Preservation of Amniotic Stem Cells in Medford, Massachusetts | Reuters">{{cite news |url=https://www.reuters.com/article/pressRelease/idUS166682+22-Oct-2009+PRN20091022 |title=European Biotech Company Biocell Center Opens First U.S. Facility for Preservation of Amniotic Stem Cells in Medford, Massachusetts &#124; Reuters |access-date=January 11, 2010 |date=October 22, 2009 |url-status=dead |archive-url=https://web.archive.org/web/20091030150358/https://www.reuters.com/article/pressRelease/idUS166682%2B22-Oct-2009%2BPRN20091022 |archive-date=October 30, 2009}}</ref><ref name="urlEuropes Biocell Center opens Medford office - Daily Business Update - The Boston Globe">{{cite news |url=http://www.boston.com/business/ticker/2009/10/europes_biocell.html |title=Europe's Biocell Center opens Medford office – Daily Business Update – The Boston Globe |access-date=January 11, 2010 | date=October 22, 2009}}</ref><ref name="urlThe Ticker - BostonHerald.com">{{cite web |url=http://www.bostonherald.com/business/general/view/20091022the_ticker |title=The Ticker |access-date=January 11, 2010}}</ref>
| After 15 weeks
|-
! scope="row" | More invasive
| [[Embryoscopy]] and [[fetoscopy]]
| Though rarely done, these involve putting a probe into a women's uterus to observe (with a video camera), or to sample blood or tissue from the embryo or fetus.||
|-
! scope="row" | More invasive
| [[Percutaneous umbilical cord blood sampling]]
| PUBS is a diagnostic genetic test that examines blood from the fetal umbilical cord to detect fetal abnormalities.
| 24–34 weeks
|}