Understanding the AFP Plus Quad Test in Pregnancy

What is the AFP PLUS® Quad Test?

It is a blood test done between the 15th and 20th weeks of pregnancy that allows us to measure certain substances that come from the developing fetus and placenta and are present in a mother’s blood. The substances that we measure are called AFP, hCG, estriol, and inhibin A. By finding out what the levels of these substances are in your blood, we learn certain things about your developing baby.

Contact Information

Division of Medical Screening and Special Testing
Women & Infants Hospital
70 Elm Street, 2nd Floor
Providence, RI 02903
P: (401) 453-7650

About the AFP Plus Quad Test

What can the AFP PLUS test tell me about my pregnancy?

It can tell you whether you have a high likelihood of having a baby with either a neural tube defect, Down syndrome, or trisomy 18. Ultimately, about one in 12 patients will have a "screen positive" AFP PLUS test result. If your test result is screen positive, it does not necessarily mean that your baby has one of these disorders, but it does mean that your doctor will suggest some additional testing.

What are neural tube defects?

Neural tube defects are a group of birth defects that include open spina bifida and anencephaly. One or two babies out of every 1,000 are born with a neural tube defect.

Open spina bifida is an incomplete closure of the spine. It varies in severity depending on where it’s located on the spine and how big the opening is. Surgery to close the opening is usually performed shortly after birth, and additional surgery is often necessary later in infancy or childhood. Open spina bifida usually causes some amount of paralysis from the waist down and interferes with bowel and bladder control. It often leads to a condition called hydrocephalus (water on the brain) and can sometimes cause mental moderate to severe developmental disability. Almost one-third of babies born with open spina bifida will not survive past age five.

Anencephaly is a very severe birth defect in which the brain and the skull fail to develop properly. It usually results in either stillbirth or death shortly after birth.

The level of AFP in the mother’s blood tends to be elevated when there is a pregnancy affected by a neural tube defect. About 90 percent of all pregnancies with open neural tube defects will be identified through AFP PLUS testing.

What is Down syndrome?

Down syndrome is a common birth defect occurring in about one in every 700 babies. It is a disorder in which an extra chromosome (the number 21 chromosome) is present in the cells of the developing fetus from the time of conception. Down syndrome usually occurs unexpectedly, and about 98 percent of the time is not inherited. Although Down syndrome occurs more frequently as mothers get older, about 75 percent of babies with Down syndrome are born to women who are younger than 35. Down syndrome is always associated with moderate to severe developmental disability, often in the mild to moderate range. Children with Down syndrome have variable but predictable physical characteristics. About 50 percent have medical problems such as heart defects. Often surgery can correct these defects. The levels of AFP and estriol in the mother’s blood tend to be low while the levels of hCG and inhibin tend to be elevated in pregnancies affected by Down syndrome. Overall, approximately 80 percent of all pregnancies with Down syndrome will be identified through the AFP PLUS Quad Test. However, detection rates vary with maternal age, ranging from 70 percent in women under 35 to more than 90 percent in women 35 and older.

What is trisomy 18?

Like Down syndrome, trisomy 18 is a birth defect caused by the presence of an extra chromosome. In this case, every cell has an extra number 18 chromosome. Trisomy 18 is much less common than Down syndrome - only one in every 8,000 babies will have it. However, like Down syndrome, it usually occurs unexpectedly and the likelihood increases as mothers get older. Trisomy 18 is a very severe birth defect. Only one in 10 babies with trisomy 18 will survive past one year of age. In the later months of pregnancy, complications such as fetal growth restriction and fetal death may occur. The levels of AFP, estriol, hCG, and inhibin in the mother’s blood tend to be low in pregnancies affected with trisomy 18. Approximately 60 to 80 percent of all pregnancies with trisomy 18 will be identified through AFP PLUS testing.

What does it mean if my AFP PLUS test result is screen positive?

A positive AFP PLUS test means that you are in a higher likelihood group for having a baby with a neural tube defect or a chromosome abnormality. However, it does not prove by itself that there is anything wrong with the pregnancy. In fact, only a small number of women with screen-positive results will have an abnormal baby. If you have a screen positive result, you should consider specific counseling to discuss further testing.

What are the tests that will be offered if my AFP PLUS test is screen positive?

It depends on your particular result. In most cases, after counseling, an ultrasound study (sonogram) will be recommended. Depending on your AFP PLUS result and the results of a sonogram, an amniocentesis or further ultrasound examination may be recommended. 

What is ultrasound and what will it show?

An ultrasound machine uses sound waves to look at the developing baby. One of the things it can do is check fetal age. Many women will have a screen positive AFP PLUS result because the dates of their pregnancies have been misjudged. When this date is adjusted, the test result may become screen negative. Occasionally twins will be discovered and will explain the screen positive result. If the gestational age is correct and you are not carrying twins, either amniocentesis or level II ultrasound may be suggested. Level II ultrasound is a detailed examination of the fetus. It cannot be used to diagnose Down syndrome or trisomy 18, but often can identify spina bifida and other fetal abnormalities.

What is amniocentesis and what will it show?

Amniocentesis is a procedure in which the doctor obtains a small sample of fluid that surrounds the developing fetus. The sample is then sent to the laboratory for testing. This fluid sample can be used to diagnose both chromosomal problems like Down syndrome and trisomy 18 as well as open defects like spina bifida. Amniocentesis is an invasive procedure, which means that there is a small risk of miscarriage (less than one in 200) associated with it. Results of the test for Down syndrome and trisomy 18 will take about seven to 14 days. Results of the test for spina bifida will take about two to five days.

What happens if a birth defect is discovered through AFP PLUS testing?

A genetic counselor will be available to discuss your baby's diagnosis in detail and the options available to you. One option would be to continue the pregnancy and make arrangements for appropriate medical services at and after delivery. Placing the infant for adoption after birth can also be considered. Another option for you to choose is the termination of pregnancy.

If my AFP PLUS test is screen negative, does that mean that my baby will be normal?

A screen negative result means that your likelihood of having a child with a neural tube defect is one in 1,000 or less. It also means that your likelihood of having a child with Down syndrome is less than that of a 35-year-old woman. It is never possible to be sure that your baby is going to be normal. The AFP PLUS Quad Test will allow us to identify at least five out of every six cases of open spina bifida and almost all cases of anencephaly. It can also lead to the diagnosis of about eight out of every 10 cases of Down syndrome and trisomy 18. Remember, a screening test can never completely rule out the possibility of a neural tube defect, Down syndrome, or trisomy 18. There are also many other birth defects that cannot be identified with this test.

What are the advantages of having the AFP PLUS test?

The test may give you and your doctor important information about your pregnancy and your developing baby. Twins may be discovered or your expected date of delivery may be corrected so that your prenatal care and visits can be adjusted accordingly.

If your baby is found to have a serious birth defect, you can receive professional counseling about how your child's physical and mental development may be affected. The individual capabilities and potential of children with birth defects are considerations that you may wish to discuss with your counselor or with other health care providers. Further information and support are available through groups such as your local Down Syndrome Society and Spina Bifida Association.

Summary

  • The AFP Plus® Quad Test is a method of screening involving the measurement of four substances in the maternal serum (serum markers). These are:
    • Alpha-fetoprotein (AFP).
    • Unconjugated oestriol (uE3).
    • Inhibin A (inhibin).
    • Human chorionic gonadotropin (hCG).
  • The test is performed between 15 and 22 weeks of pregnancy.
  • The four serum markers are used together with the woman’s age to estimate her likelihood of having a pregnancy with Down syndrome. Women with a mid-pregnancy risk of one in 270 or greater are interpreted as screen positive and offered further tests. About 7 percent of all women screened will fall into the screen-positive group, and about one in 60 of these will have an affected pregnancy.
  • The level of AFP alone is used to determine whether there is an increased likelihood of having a pregnancy with an open neural tube defect. Women with a raised AFP level (at least two times the normal median) are interpreted as screen positive and offered further tests. About 2.5 percent of all women screened will fall into the screen-positive group, and about one in 25 of these will have an affected pregnancy.
  • The Quad Test identifies about 80 percent of Down syndrome pregnancies, 90 percent of open spina bifida pregnancies, and nearly all pregnancies with anencephaly.
  • The Quad Test components, AFP, uE3, and hCG, will also identify pregnancies at high risk of trisomy 18. The test identifies approximately six out of 10 women who have pregnancies with trisomy 18.
  • Providing relevant information to patients with understanding and confidence is critical. However good the technical aspects of a screening service, its quality will always depend on how well the test is explained and the extent to which women feel that they have made the right choice.