Editing Triple test

{{Short description|Investigation performed during pregnancy in the 2nd trimester to check chromosomal abnormalities}}
{{distinguish|text=[[Triple test score]], a diagnostic tool for examining potentially cancerous breasts}}
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{{Infobox diagnostic
| name            = Triple test
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| test of         =chromosomal abnormalities
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| synonyms        = Triple  screen,Bart's test
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The '''triple test''', also called  '''triple screen''', the '''Kettering test''' or the '''Bart's test''', is an investigation performed during [[pregnancy]] in the second trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities (and neural tube defects).

The term "multiple-marker screening test" is sometimes used instead.<ref name="pmid9572446">{{cite journal |vauthors=Renier MA, Vereecken A, Van Herck E, Straetmans D, Ramaekers P, Buytaert P |title=Second trimester maternal dimeric inhibin-A in the multiple-marker screening test for Down's syndrome |journal=Hum. Reprod. |volume=13 |issue=3 |pages=744–8 |date=March 1998 |pmid=9572446 |doi= 10.1093/humrep/13.3.744|url=http://humrep.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9572446|doi-access=free }}</ref><ref name="pmid14586337">{{cite journal |vauthors=Yudin MH, Prosen TL, Landers DV |title=Multiple-marker screening in human immunodeficiency virus-positive pregnant women: Screen positivity rates with the triple and quad screens |journal=Am. J. Obstet. Gynecol. |volume=189 |issue=4 |pages=973–6 |date=October 2003 |pmid=14586337 |doi= 10.1067/S0002-9378(03)01053-6}}</ref> This term can encompass the "double test" and "quadruple test" (described below).

The Triple screen measures [[Blood serum|serum]] levels of [[Alpha-fetoprotein|AFP]], [[estriol]], and [[beta-hCG]], with a 70% [[sensitivity and specificity|sensitivity]] and 5% [[false-positive]] rate.  It is complemented in some regions of the United States, as the ''Quad screen'' (adding inhibin A to the panel, resulting in an 81% sensitivity and 5% false-positive rate for detecting [[Down syndrome]] when taken at 15–18 weeks of [[Gestational age (obstetrics)|gestational age]])<ref>{{cite journal|doi = 10.1258/jms.2009.009017|title= The ability of the quadruple test to predict adverse perinatal outcomes in a high-risk obstetric population|pmid=    19564516|last1 = Lao|first1 =  M.R.|last2 = Calhoun|first2= B. C.|last3 =  Bracero|first3= L. A.|last4 = Wang|first4= Y.|last5= Seybold|first5= D. J.|last6= Broce |first6=M.|last7= Hatjis |first7=C. G.|journal=J Med Screen|year=2009|volume=16|issue=2|pages=55–59 |s2cid= 23214929}}</ref> and other [[prenatal diagnosis]] techniques, although it remains widely used in Canada<ref>[http://www.sogc.org/health/pregnancy-prenatal_e.asp sogc.org] {{Webarchive|url=https://web.archive.org/web/20090628121155/http://www.sogc.org/health/pregnancy-prenatal_e.asp |date=2009-06-28 }}</ref> and other countries. A positive screen indicates an increased risk of chromosomal abnormalities (and neural tube defects), and such patients are then referred for more sensitive and specific procedures to receive a definitive diagnosis, often prenatal diagnosis via [[amniocentesis]], although the stronger screening option of [[cell-free fetal DNA]] screening (also popularly known as noninvasive prenatal screening) is frequently offered. The Triple test can be understood as an early predecessor to a long line of subsequent technological improvements.  In some American states, such as Missouri, Medicaid reimburses only for the Triple test and not other potentially more accurate screening tests, whereas California offers Quad tests to all pregnant women.<ref>[http://www.cdph.ca.gov/programs/pns/Documents/Provider%20Handbook%20%202009%20WEB.pdf cdph.ca.gov] {{Webarchive|url=https://web.archive.org/web/20170212001459/http://www.cdph.ca.gov/programs/pns/Documents/Provider%20Handbook%20%202009%20WEB.pdf |date=2017-02-12 }}</ref>

While the triple test can be performed at any point between 15 and 21.9 weeks of gestation, the highest detection rate for open neural defects is given by a test performed between 16 and 18 weeks of gestation.<ref>{{cite web |title=Understanding the Triple Test |url=https://www.sonoraquest.com/patient/knowledge-center/understanding-the-triple-test/ |website=Sonora Quest Laboratories |access-date=1 February 2023}}</ref>

==Conditions screened==
The most common abnormality the test can screen is [[trisomy 21]] ([[Down syndrome]]). In addition to Down syndrome, the triple and quadruple screens assess risk for fetal [[trisomy 18]] also known as [[Edwards syndrome]], open [[neural tube defects]], and may also detect an increased risk of [[Turner syndrome]], [[triploidy]], [[trisomy 16]] mosaicism, [[fetal death]], [[Smith–Lemli–Opitz syndrome]], and [[steroid sulfatase deficiency]].<ref name="pmid12135803">{{cite journal |author=Benn PA |title=Advances in prenatal screening for Down syndrome: I. general principles and second trimester testing |journal=Clin. Chim. Acta |volume=323 |issue=1–2 |pages=1–16 |year=2002 |pmid=12135803 |doi=10.1016/S0009-8981(02)00186-9}}</ref>

==Values measured==
The triple test measures the following three levels in the maternal serum:<ref name="pmid17601890">{{cite journal  |vauthors=Ball RH, Caughey AB, Malone FD, etal |title=First- and second-trimester evaluation of risk for Down syndrome |journal=Obstet Gynecol |volume=110 |issue=1 |pages=10–7 |year=2007 |pmid=17601890 |doi=10.1097/01.AOG.0000263470.89007.e3|s2cid=10885982 }}</ref>

# [[alpha-fetoprotein]] (AFP)
# [[human chorionic gonadotropin]] (hCG)
# unconjugated [[estriol]] (UE<sub>3</sub>)

==Interpretation==
The levels may indicate increased risk for certain conditions or may be benign:

{| class="wikitable"
| '''[[alpha-fetoprotein|AFP]]''' || '''UE<sub>3</sub>''' || '''[[Human chorionic gonadotropin|hCG]]''' || '''Associated conditions''' 
 |- 
 | low || low || high || [[Down syndrome]]
 |- 
 | low || low || low  || [[trisomy 18]] ([[Edward's syndrome]])
 |- 
 | high || n/a || n/a  || [[neural tube defects]] (like [[spina bifida]] that may have associated increased levels of [[acetylcholinesterase]] in the amnionic fluid), [[omphalocele]], [[gastroschisis]], [[multiple gestation]] (like [[twins]] or [[Multiple birth|triplets]]), or an underestimation of [[Gestational age (obstetrics)|gestational age]].
|}

An estimated risk is calculated and adjusted for the expectant mother's [[Ageing|age]];<ref name="titleDowns Syndrome Screening at Nottingham City Hospital">{{cite web |url=http://www.nuh.nhs.uk/nch/clinpath/resources/downs/default.htm |title=Downs Syndrome Screening at Nottingham City Hospital |accessdate=2007-12-20 |url-status=dead |archive-url=https://web.archive.org/web/20080612221254/http://www.nuh.nhs.uk/nch/clinpath/resources/downs/default.htm |archive-date=2008-06-12 }}</ref> if she is diabetic; if she is having twins or other multiples, and the gestational age of the fetus. Weight and ethnicity may also be used in adjustments.<ref name="ReferenceA">Henry's Clinical Diagnosis and Management by Laboratory Methods, 22nd ed. Chapter 25</ref> Many of these factors affect the levels of the substances being measured and the interpretation of the results:<ref name="ReferenceA"/>

* As maternal weight increases, [[MSAFP]] level decreases
* African-American women have [[MSAFP]] levels that are 10-15% higher than those of Caucasian women for unknown reasons 
* Women with insulin-dependent diabetes mellitus have MSAFP levels that are 20% lower than the rest of the population
* Having multiple gestations, such as twins, increases MSAFP because each fetus secretes its own AFP
* Incorrect estimation of gestational age is the most common cause of abnormal MSAFP levels
[[File:Prenatal Down syndrome screening algorithm.png|thumb|An example of an algorithm for indications for further testing depending on the outcome of non-genetic blood tests including the triple test.<ref>Diagram by Mikael Häggström, using following source: {{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|author=Jacquelyn V Halliday |author2=Geralyn M Messerlian |author3=Glenn E Palomaki }} This topic last updated: Feb 16, 2023.</ref>]]
The test is for [[Screening (medicine)|screening]], not for [[medical diagnosis|diagnosis]],<ref name="pmid18041410">{{cite journal |vauthors=Lamlertkittikul S, Chandeying V |title=Experience on triple markers serum screening for Down syndrome fetus in Hat Yai, Regional Hospital |journal=J Med Assoc Thai |volume=90 |issue=10 |pages=1970–6 |year=2007 |pmid=18041410 }}</ref> and does not have nearly the same predictive power as that of genetic blood testing (testing [[cell-free fetal DNA]], or invasive [[genetic testing]] which are performed by [[amniocentesis]] or [[chorionic villus sampling]]. The screening test carries a much lower risk to the [[fetus]] than invasive testing, however, and in conjunction with the age-related risk of the patient it is useful to help determine the need for more invasive tests.

==Variations==

If only two of the hormones above are tested for, then the test is called a double test. A quad test tests an additional hormone, [[inhibin]]. Furthermore, the triple test may be combined with an [[ultrasound]] measurement of [[nuchal translucency]]. {{Citation needed|date=December 2007}}

===Double test===
Free beta hCG and [[Pregnancy-associated plasma protein A|PAPP-A]] are measured. However, the maternal age, weight, ethnicity etc. are still included. In the UK the double test is part of the combined test for prenatal diagnostics.<ref>{{Cite web|url=https://www.nice.org.uk/guidance/cg62/chapter/Key-priorities-for-implementation|title=Antenatal care for uncomplicated pregnancies|date=26 March 2008 |publisher=National Institute for Health and Care Excellende|access-date=10 October 2016}}</ref>

===Quadruple test===
A test of levels of dimeric [[inhibin]] A (DIA) is sometimes added to the other three tests, under the name "quadruple test."<ref name="pmid16700087">{{cite journal |vauthors=Wald NJ, Morris JK, Ibison J, Wu T, George LM |title=Screening in early pregnancy for pre-eclampsia using Down syndrome quadruple test markers |journal=Prenat. Diagn. |volume=26 |issue=6 |pages=559–64 |year=2006 |pmid=16700087 |doi=10.1002/pd.1459|s2cid=1751873 }}</ref> Other names used include "quad test", "quad screen", or "tetra screen."  Inhibin A will be found high in cases of trisomy 21 and unchanged in cases of trisomy 18.<ref name="pmid11494294">{{cite journal |vauthors=Spencer K, Liao AW, Ong CY, Flack NJ, Nicolaides KH |title=Maternal serum activin A and inhibin A in trisomy 18 pregnancies at 10-14 weeks |journal=Prenat Diagn. |volume=21 |issue=7 |pages=571–574 |year=2001 |pmid=11494294 |doi=10.1002/pd.125|s2cid=32154357 }}</ref>

{| class="wikitable"
| '''[[Inhibin]] A''' || '''Associated conditions''' 
 |- 
 | High || [[Trisomy 21]] (Down syndrome)
 |- 
 | Unchanged || [[Trisomy 18]] (Edwards syndrome)
 |-
 | Variable || [[Trisomy 13]] (Patau syndrome)
|}

==See also==
* [[Triple bolus test]]
* [[Cell free fetal DNA]] test

==References==
{{reflist|2}}

==External links==
* [http://www.americanpregnancy.org/prenataltesting/tripletest.html AmericanPregnancy.org]
* [https://web.archive.org/web/20060102073530/http://www.jr2.ox.ac.uk/bandolier/band111/b111-5.html Risk and Down screening]

{{Obstetrical procedures}}

{{DEFAULTSORT:Triple Test}}
[[Category:Tests during pregnancy]]