The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

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 screen measures serum levels of AFP,

estriol Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estrone. Levels of estriol in women who are not pregnant are almost ...

, and

beta-hCG Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantatio ...

, with a 70% sensitivity and 5%

false-positive A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result ...

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 Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...

when taken at 15–18 weeks of

gestational age In obstetrics, gestational age is a measure of the age of a pregnancy which is taken from the beginning of the woman's last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method if available. Suc ...

) and other

prenatal diagnosis Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of ...

techniques, although it remains widely used in Canada 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 Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ne ...

, although the stronger screening option of

cell-free fetal DNA Cell-free fetal DNA (cffDNA) is fetal DNA that circulates freely in the maternal blood. Maternal blood is sampled by venipuncture. Analysis of cffDNA is a method of non-invasive prenatal diagnosis frequently ordered for pregnant women of advanced ...

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.

Conditions screened

The most common abnormality the test can screen is

trisomy 21 A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes). Description and causes Most organisms that reprodu ...

(

). In addition to Down syndrome, the triple and quadruple screens assess risk for fetal

trisomy 18 A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes). Description and causes Most organisms that reprodu ...

also known as Edward's syndrome, open

neural tube defects Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo b ...

, and may also detect an increased risk of

Turner syndrome Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hair ...

triploidy Polyploidy is a condition in which the cells of an organism have more than one pair of ( homologous) chromosomes. Most species whose cells have nuclei ( eukaryotes) are diploid, meaning they have two sets of chromosomes, where each set contain ...

trisomy 16 Trisomy 16 is a chromosomal abnormality in which there are 3 copies of chromosome 16 rather than two. It is the most common trisomy leading to miscarriage and the second most common chromosomal cause of it, closely following X-chromosome monosomy ...

mosaicism,

fetal death Perinatal mortality (PNM) refers to the death of a fetus or neonate and is the basis to calculate the perinatal mortality rate. Variations in the precise definition of the perinatal mortality exist, specifically concerning the issue of inclusion o ...

Smith–Lemli–Opitz syndrome Smith–Lemli–Opitz syndrome is an inborn error of cholesterol synthesis. It is an autosomal recessive, multiple malformation syndrome caused by a mutation in the enzyme 7-Dehydrocholesterol reductase encoded by the DHCR7 gene. It causes a bro ...

, and

steroid sulfatase deficiency A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

Values measured

The triple test measures the following three levels in the maternal serum: #

alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...

(AFP) #

human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...

(hCG) # unconjugated

(UE₃)

Interpretation

The levels may indicate increased risk for certain conditions or may be benign: An estimated risk is calculated and adjusted for the expectant mother's

age Age or AGE may refer to: Time and its effects * Age, the amount of time someone or something has been alive or has existed ** East Asian age reckoning, an Asian system of marking age starting at 1 * Ageing or aging, the process of becoming older ...

; 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.Henry's Clinical Diagnosis and Management by Laboratory Methods, 22nd ed. Chapter 25 Many of these factors affect the levels of the substances being measured and the interpretation of the results: * 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 The test is for

screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...

, not for

diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...

, and does not have nearly the same predictive power of

chorionic villus sampling Chorionic villus sampling (CVS), sometimes called "chorionic ''villous'' sampling" (as "villous" is the adjectival form of the word "villus"), is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It ent ...

. The screening test carries a much lower risk to the

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...

, 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 Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...

. Furthermore, the triple test may be combined with an

ultrasound Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...

measurement of nuchal translucency.

Double test

Free beta hCG and

PAPP-A Pappalysin-1, also known as pregnancy-associated plasma protein A, and insulin-like growth factor binding protein-4 protease is a protein encoded by the ''PAPPA'' gene in humans. PAPPA is a secreted protease whose main substrate is insulin-like gro ...

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.

Quadruple test

A test of levels of dimeric

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 will be found high in cases of trisomy 21 and unchanged in cases of trisomy 18.

References

External links

AmericanPregnancy.org

{{DEFAULTSORT:Triple Test Tests during pregnancy