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.[1][2] This term can encompass the "double test" and "quadruple test" (described below).
The Triple test measures serum levels of AFP, estriol, and beta-hCG, with a 70% sensitivity 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)[3] and other prenatal diagnosis techniques, although it remains widely used in Canada[4] 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. 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.[5]
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The most common abnormality the test can screen is trisomy 21 (Down syndrome). 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, and may also detect an increased risk of Turner syndrome, triploidy, trisomy 16 mosaicism, fetal death, Smith-Lemli-Opitz syndrome, and steroid sulfatase deficiency.[6]
The triple test measures the following three levels in the maternal serum:[7]
The levels may indicate increased risk for certain conditions:
AFP | UE3 | 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 associated with increase levels of acetylcholinesterase in aminonic fluid, or omphalocele, or gastroschisis, or multiple gestation like twins or triplets |
An estimated risk is calculated and adjusted for the expectant mother's age;[8] 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, not for diagnosis,[9] and does not have nearly the same predictive power of amniocentesis or chorionic villus sampling. The screening test carries a much lower risk to the fetus, however, and in conjunction with the age-related risk of the patient it is useful to help determine the need for more invasive tests.
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.
3.0 Normal 3.1 Normal 3.5 Normal 4.0 Normal 4.7 Normal 5.0 Normal 5.1 Abnormal
A test of levels of dimeric inhibin A (DIA) is sometimes added to the other three tests, under the name "quadruple test."[10] 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.
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