Triple test
Encyclopedia
The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 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. This term can encompass the "double test" and "quadruple test" (described below).

The Triple test measures serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...

 levels of AFP
Alpha-fetoprotein
Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene....

, estriol
Estriol
Estriol is one of the three main estrogens produced by the human body.-Synthesis:Estriol is only produced in significant amounts during pregnancy as it is made by the placenta from 16-Hydroxydehydroepiandrosterone sulfate , an androgen steroid made in the fetal liver and adrenal glands.The human...

, and beta-hCG, with a 70% sensitivity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

 and 5% false-positive rate. It is complemented in some regions of the United States, as the Quad test (adding inhibin A to the panel, resulting in an 81% sensitivity and 5% false-positive rate for detecting Down syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...

) and other prenatal diagnosis
Prenatal diagnosis
Prenatal diagnosis or prenatal screening is testing for diseases or conditions in a fetus or embryo before it is born. The aim is to detect birth defects such as neural tube defects, Down syndrome, chromosome abnormalities, genetic diseases and other conditions, such as spina bifida, cleft palate,...

 techniques, although it remains widely used in Canada and other countries. A positive test means having a high 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, mostly invasive procedures like amniocentesis
Amniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...

. 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.

Conditions screened

The most common abnormality the test can screen is trisomy 21 (Down syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...

). In addition to Down syndrome, the triple and quadruple tests screen for fetal trisomy 18 also known as Edward's syndrome, open neural tube defects
Neural tube defects
Neural tube defects are one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In the 2nd week of pregnancy called gastrulation, specialized cells...

, and may also detect an increased risk of Turner syndrome
Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...

, triploidy, trisomy 16
Trisomy 16
Trisomy 16 is a chromosomal abnormality in which there are three copies of chromosome 16 rather than two. It is the most common chromosomal cause of miscarriage during the first trimester of pregnancy....

 mosaicism, fetal death, Smith-Lemli-Opitz syndrome
Smith-Lemli-Opitz syndrome
Smith-Lemli-Opitz syndrome is an autosomal recessive metabolic and developmental congenital disorder that causes the inability to correctly produce or synthesize cholesterol due to a low occurrence of the 7-DHC reductace enzyme.-Symptoms:The signs and symptoms of SLOS syndrome vary widely...

, and steroid sulfatase deficiency.

Values measured

The triple test measures the following three levels in the maternal serum:
  • alpha-fetoprotein
    Alpha-fetoprotein
    Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene....

     (AFP)
  • human chorionic gonadotropin
    Human chorionic gonadotropin
    Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...

     (hCG)
  • unconjugated estriol
    Estriol
    Estriol is one of the three main estrogens produced by the human body.-Synthesis:Estriol is only produced in significant amounts during pregnancy as it is made by the placenta from 16-Hydroxydehydroepiandrosterone sulfate , an androgen steroid made in the fetal liver and adrenal glands.The human...

     (UE3)

Interpretation

The levels may indicate increased risk for certain conditions:
AFP
Alpha-fetoprotein
Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene....

UE3 hCG
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...

Associated conditions
>-
| low
low high Down Syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...


>-
| low
low low >-
| high
n/a n/a neural tube defects
Neural tube defects
Neural tube defects are one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In the 2nd week of pregnancy called gastrulation, specialized cells...

 like spina bifida
Spina bifida
Spina bifida is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to protrude through...

 associated with increase levels of acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...

 in aminonic fluid, or omphalocele
Omphalocele
An omphalocele is a type of abdominal wall defect in which the intestines, liver, and occasionally other organs remain outside of the abdomen in a sac because of a defect in the development of the muscles of the abdominal wall.-Presentation:The sac, which is formed from an outpouching of...

, or gastroschisis
Gastroschisis
Gastroschisis represents a congenital defect characterized by a defect in the anterior abdominal wall through which the abdominal contents freely protrude. There is no overlying sac and the size of the defect is usually less than 4 cm...

, or multiple gestation like twins
TWINS
Two Wide-Angle Imaging Neutral-Atom Spectrometers are a pair of NASA instruments aboard two United States National Reconnaissance Office satellites in Molniya orbits. TWINS was designed to provide stereo images of the Earth's ring current. The first instrument, TWINS-1, was launched aboard USA-184...

 or triplets
Multiple birth
A multiple birth occurs when more than one fetus is carried to term in a single pregnancy. Different names for multiple births are used, depending on the number of offspring. Common multiples are two and three, known as twins and triplets...



An estimated risk is calculated and adjusted for the expectant mother's age
Ageing
Ageing or aging is the accumulation of changes in a person over time. Ageing in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of ageing grow and expand over time, while others decline...

; if she's diabetic; if she's having twins or other multiples, and the gestational age of the fetus. Weight and ethnicity may also be used in adjustments. Many of these factors affect the levels of the substances being measured and the interpretation of the results.

The test is for screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

, not for diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

, and does not have nearly the same predictive power of amniocentesis
Amniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...

 or chorionic villus sampling
Chorionic villus sampling
Chorionic villus sampling , sometimes misspelled "chorionic villous sampling", is a form of prenatal diagnosis to determine chromosomal or genetic disorders in the fetus. It entails sampling of the chorionic villus and testing it...

. The screening test carries a much lower risk to the fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...

, however, and in conjunction with the age-related risk of the patient it is useful to help determine the need for more invasive tests.

Triple Test Result

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
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...

 measurement of nuchal translucency.

3.0 Normal
3.1 Normal
3.5 Normal
4.0 Normal
4.7 Normal
5.0 Normal
5.1 Abnormal

Quadruple test

A test of levels of dimeric inhibin A (DIA) is sometimes added to the other three tests, under the name "quadruple test." Other names used include "quad test", "quad screen", or "tetra screen." Inhibin A (DIA) will be found high in cases of Trisomy 21 and low in cases of Trisomy 18.

External links

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