These tests (beta test or double test, alpha test or triple test, and quadruple test) are performed on pregnant women in the 2nd trimester of pregnancy to detect possible genetic malformations or serious chromosomal/genetic abnormalities. These screening tests may indicate the possibility of fetal abnormalities (mainly trisomy 21 [Down syndrome] or trisomy 18). They may also indicate the possibility of neural tube abnormalities (e.g., myelomeningocele, spina bifida) or abdominal wall lesions (umbilical hernia or gastroschisis).
The incidence of these abnormalities is directly related to the age of the mother. These tests are performed on all pregnant women, usually in the second trimester of pregnancy, but they are screening tests and not diagnostic tests. If the screening results are positive, then more direct, and definitive tests can be performed, such as chorionic villus sampling (CVS) in early pregnancy or amniocentesis in mid-pregnancy. Most pregnant women over 35 usually have chorionic villus sampling or amniocentesis without maternal prenatal screening tests.
There are several variations of maternal prenatal screening tests:
Double test or beta test two biomarkers are measured: human beta chorionic gonadotropin (β-hCG) and alpha-fetoprotein (αFP).
Triple test or alpha test three biomarkers are measured: human beta chorionic gonadotropin (β-hCG), αFP, and estriol. αFP is produced in the yolk sac and fetal liver. Unconjugated estriol (free) and β-hCG are produced by the placenta.
Quadruple test four biomarkers are measured: β-hCG, αFP, estriol, and inhibin A.
In the Comprehensive Maternal Prenatal Screening tests, αFP, fetal nuchal translucency (ultrasound), β-hCG, and total hCG as well as pregnancy-associated plasma protein-A (PAPP-A) are measured.
A triple test in the mother offers a 50% to 80% chance of detecting trisomy 21 compared to measuring αFP alone which has a 30% chance of detection. What is now recommended is the quadruple test which is usually combined with fetal nuchal translucency (FTN). These tests are most accurately performed during the second trimester of pregnancy and more specifically between the 14th and 24th week (ideally between the 16th and 18th week) of pregnancy. The use of ultrasound to determine the exact gestational age improves the sensitivity and specificity of Maternal Prenatal Screening tests.
Screening for birth defects in the first trimester should include fetal cervical transparency in combination with β-hCG and pregnancy-associated plasma protein-A (PAPP-A). A low PAPP-A level may indicate an increased risk of stillbirth. These tests have detection rates comparable to the standard second-trimester triple test.
First-trimester screening (11th to 13th weeks) offers several potential advantages over second-trimester screening. When test results are negative it can help reduce the mother's anxiety sooner. If the results are positive, it allows women to take advantage of first-trimester prenatal diagnosis with trophoblast retrieval at the 10th to 12th weeks or amniocentesis in early pregnancy. Detecting the problem earlier in pregnancy allows women to prepare better for the birth of a child with health problems and offers women greater protection and less risk to their health if they choose to terminate the pregnancy. In first-trimester tests, neural tube abnormalities cannot be determined.
In trisomy 21, second-trimester maternal serum measurements of αFP and unconjugated (free) estriol levels are approximately 25% below normal, and serum hCG levels are approximately twice normal. Test results are expressed as multiples of the mean (MoM). The values of αFP and estriol (E3) during pregnancy with trisomy 21 are lower than those with normal pregnancy, which means that the values below the average are below 1 MoM. The hCG value for trisomy 21 is above 1 MoM. MoM values, fetal age, and maternal weight are used to calculate the potential risk for chromosomal abnormalities (e.g., trisomy 21).
Inhibin A is normally secreted by granulosa cells in the ovaries and inhibits the production of follicle-stimulating hormone (FSH) by the pituitary gland. Inhibin A is a glycoprotein of placental origin in pregnancy similar to hCG. Its levels in the mother's serum remain relatively stable until the 15th to 18th week of pregnancy. Inhibin A is important in the control of fetal development. Serum levels of inhibin A are twice as high in pregnancies with trisomy 21 compared to normal pregnancies. The discovery of this fact led to the inclusion of inhibin A in screening tests for trisomy 21. Inhibin A levels are significantly lower in women with normal pregnancies than in women with pregnancies that result in miscarriage.
Preparing the Patient for the Examination
- Fasting is not required before the test.
- On the day of the examination, the ultrasound gestational age and some other details of the ultrasound, woman's weight and some details of her personal history must be known.
